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Start Over Author "Levings, Megan K." Journal european journal of immunology
34 results on '"Levings, Megan K."'

2. PTEN is required for human Treg suppression of costimulation in vitro

Author

Lam, Avery J., primary, Haque, Manjurul, additional, Ward‐Hartstonge, Kirsten A., additional, Uday, Prakruti, additional, Wardell, Christine M., additional, Gillies, Jana K., additional, Speck, Madeleine, additional, Mojibian, Majid, additional, Klein Geltink, Ramon I., additional, and Levings, Megan K., additional

Published
2022
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3. Guidelines for standardizing T-cell cytometry assays to link biomarkers, mechanisms, and disease outcomes in type 1 diabetes

Author

Yang, Jennie H. M., Ward‐Hartstonge, Kirsten A., Perry, Daniel J., Blanchfield, J. Lori, Posgai, Amanda L., Wiedeman, Alice E., Diggins, Kirsten, Rahman, Adeeb, Tree, Timothy I. M., Brusko, Todd M., Levings, Megan K., James, Eddie A., Kent, Sally C., Speake, Cate, Homann, Dirk, and Long, S. Alice

Subjects
Diabetes Mellitus, Type 1, T-Lymphocytes, Immunology, Immunology and Allergy, Humans, Flow Cytometry, Biomarkers, Article, Immunophenotyping
Abstract

Cytometric immunophenotyping is a powerful tool to discover and implement T-cell biomarkers of type 1 diabetes (T1D) progression and response to clinical therapy. Although many discovery-based T-cell biomarkers have been described, to date, no such markers have been widely adopted in standard practice. The heterogeneous nature of T1D and lack of standardized assays and experimental design across studies is a major barrier to the broader adoption of T-cell immunophenotyping assays. There is an unmet need to harmonize the design of immunophenotyping assays, including those that measure antigen-agnostic cell populations, such that data collected from different clinical trial sites and T1D cohorts are comparable, yet account for cohort-specific features and different drug mechanisms of action. In these Guidelines, we aim to provide expert advice on how to unify aspects of study design and practice. We provide recommendations for defining cohorts, method implementation, as well as tools for data analysis and reporting by highlighting and building on selected successes. Harmonization of cytometry-based T-cell assays will allow researchers to better integrate findings across trials, ultimately enabling the identification and validation of biomarkers of disease progression and treatment response in T1D.

Published
2021

4. Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

Author

Cossarizza, Andrea, primary, Chang, Hyun‐Dong, additional, Radbruch, Andreas, additional, Abrignani, Sergio, additional, Addo, Richard, additional, Akdis, Mübeccel, additional, Andrä, Immanuel, additional, Andreata, Francesco, additional, Annunziato, Francesco, additional, Arranz, Eduardo, additional, Bacher, Petra, additional, Bari, Sudipto, additional, Barnaba, Vincenzo, additional, Barros‐Martins, Joana, additional, Baumjohann, Dirk, additional, Beccaria, Cristian G., additional, Bernardo, David, additional, Boardman, Dominic A., additional, Borger, Jessica, additional, Böttcher, Chotima, additional, Brockmann, Leonie, additional, Burns, Marie, additional, Busch, Dirk H., additional, Cameron, Garth, additional, Cammarata, Ilenia, additional, Cassotta, Antonino, additional, Chang, Yinshui, additional, Chirdo, Fernando Gabriel, additional, Christakou, Eleni, additional, Čičin‐Šain, Luka, additional, Cook, Laura, additional, Corbett, Alexandra J., additional, Cornelis, Rebecca, additional, Cosmi, Lorenzo, additional, Davey, Martin S., additional, De Biasi, Sara, additional, De Simone, Gabriele, additional, del Zotto, Genny, additional, Delacher, Michael, additional, Di Rosa, Francesca, additional, Di Santo, James, additional, Diefenbach, Andreas, additional, Dong, Jun, additional, Dörner, Thomas, additional, Dress, Regine J., additional, Dutertre, Charles‐Antoine, additional, Eckle, Sidonia B. G., additional, Eede, Pascale, additional, Evrard, Maximilien, additional, Falk, Christine S., additional, Feuerer, Markus, additional, Fillatreau, Simon, additional, Fiz‐Lopez, Aida, additional, Follo, Marie, additional, Foulds, Gemma A., additional, Fröbel, Julia, additional, Gagliani, Nicola, additional, Galletti, Giovanni, additional, Gangaev, Anastasia, additional, Garbi, Natalio, additional, Garrote, José Antonio, additional, Geginat, Jens, additional, Gherardin, Nicholas A., additional, Gibellini, Lara, additional, Ginhoux, Florent, additional, Godfrey, Dale I., additional, Gruarin, Paola, additional, Haftmann, Claudia, additional, Hansmann, Leo, additional, Harpur, Christopher M., additional, Hayday, Adrian C., additional, Heine, Guido, additional, Hernández, Daniela Carolina, additional, Herrmann, Martin, additional, Hoelsken, Oliver, additional, Huang, Qing, additional, Huber, Samuel, additional, Huber, Johanna E., additional, Huehn, Jochen, additional, Hundemer, Michael, additional, Hwang, William Y. K., additional, Iannacone, Matteo, additional, Ivison, Sabine M., additional, Jäck, Hans‐Martin, additional, Jani, Peter K., additional, Keller, Baerbel, additional, Kessler, Nina, additional, Ketelaars, Steven, additional, Knop, Laura, additional, Knopf, Jasmin, additional, Koay, Hui‐Fern, additional, Kobow, Katja, additional, Kriegsmann, Katharina, additional, Kristyanto, H., additional, Krueger, Andreas, additional, Kuehne, Jenny F., additional, Kunze‐Schumacher, Heike, additional, Kvistborg, Pia, additional, Kwok, Immanuel, additional, Latorre, Daniela, additional, Lenz, Daniel, additional, Levings, Megan K., additional, Lino, Andreia C., additional, Liotta, Francesco, additional, Long, Heather M., additional, Lugli, Enrico, additional, MacDonald, Katherine N., additional, Maggi, Laura, additional, Maini, Mala K., additional, Mair, Florian, additional, Manta, Calin, additional, Manz, Rudolf Armin, additional, Mashreghi, Mir‐Farzin, additional, Mazzoni, Alessio, additional, McCluskey, James, additional, Mei, Henrik E., additional, Melchers, Fritz, additional, Melzer, Susanne, additional, Mielenz, Dirk, additional, Monin, Leticia, additional, Moretta, Lorenzo, additional, Multhoff, Gabriele, additional, Muñoz, Luis Enrique, additional, Muñoz‐Ruiz, Miguel, additional, Muscate, Franziska, additional, Natalini, Ambra, additional, Neumann, Katrin, additional, Ng, Lai Guan, additional, Niedobitek, Antonia, additional, Niemz, Jana, additional, Almeida, Larissa Nogueira, additional, Notarbartolo, Samuele, additional, Ostendorf, Lennard, additional, Pallett, Laura J., additional, Patel, Amit A., additional, Percin, Gulce Itir, additional, Peruzzi, Giovanna, additional, Pinti, Marcello, additional, Pockley, A. Graham, additional, Pracht, Katharina, additional, Prinz, Immo, additional, Pujol‐Autonell, Irma, additional, Pulvirenti, Nadia, additional, Quatrini, Linda, additional, Quinn, Kylie M., additional, Radbruch, Helena, additional, Rhys, Hefin, additional, Rodrigo, Maria B., additional, Romagnani, Chiara, additional, Saggau, Carina, additional, Sakaguchi, Shimon, additional, Sallusto, Federica, additional, Sanderink, Lieke, additional, Sandrock, Inga, additional, Schauer, Christine, additional, Scheffold, Alexander, additional, Scherer, Hans U., additional, Schiemann, Matthias, additional, Schildberg, Frank A., additional, Schober, Kilian, additional, Schoen, Janina, additional, Schuh, Wolfgang, additional, Schüler, Thomas, additional, Schulz, Axel R., additional, Schulz, Sebastian, additional, Schulze, Julia, additional, Simonetti, Sonia, additional, Singh, Jeeshan, additional, Sitnik, Katarzyna M., additional, Stark, Regina, additional, Starossom, Sarah, additional, Stehle, Christina, additional, Szelinski, Franziska, additional, Tan, Leonard, additional, Tarnok, Attila, additional, Tornack, Julia, additional, Tree, Timothy I. M., additional, van Beek, Jasper J. P., additional, van de Veen, Willem, additional, van Gisbergen, Klaas, additional, Vasco, Chiara, additional, Verheyden, Nikita A., additional, von Borstel, Anouk, additional, Ward‐Hartstonge, Kirsten A., additional, Warnatz, Klaus, additional, Waskow, Claudia, additional, Wiedemann, Annika, additional, Wilharm, Anneke, additional, Wing, James, additional, Wirz, Oliver, additional, Wittner, Jens, additional, Yang, Jennie H. M., additional, and Yang, Juhao, additional

Published
2021
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6. Acidity promotes the differentiation of immunosuppressive regulatory T cells.

Author

Tuomela, Karoliina and Levings, Megan K

Subjects
REGULATORY T cells, LACTIC acid, T cells, CELL populations, ACIDITY
Abstract

The metabolic milieu is emerging as a major contributing factor in the maintenance of the immunosuppressive microenvironment within tumors. In particular, the presence of lactic acid produced by highly glycolytic cancer cells is known to suppress antitumor immune cell subsets while promoting immunosuppressive cell populations, such as regulatory T cells (Tregs). Unlike conventional T cells, Tregs have a unique, potent ability to take up lactic acid to fuel both mitochondrial metabolism and gluconeogenesis, thus supporting suppressive function and proliferation. In this issue of the European Journal of Immunology [Eur. J. Immunol. 2023.53:2250258], Rao et al. uncover a novel mechanism by which lactic acid can support Treg accumulation within tumors in mice. This study shows that lactic acid, through a pH‐dependent mechanism rather than lactate itself, promotes TGFβ‐induced differentiation of Tregs from conventional CD4+ T cells. These findings build on the already multifaceted role of lactic acid in maintaining an immunosuppressive tumor microenvironment. [ABSTRACT FROM AUTHOR]

Published
2023
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8. Guidelines for standardizing T‐cell cytometry assays to link biomarkers, mechanisms, and disease outcomes in type 1 diabetes.

Author

Yang, Jennie H. M., Ward‐Hartstonge, Kirsten A., Perry, Daniel J., Blanchfield, J. Lori, Posgai, Amanda L., Wiedeman, Alice E., Diggins, Kirsten, Rahman, Adeeb, Tree, Timothy I. M., Brusko, Todd M., Levings, Megan K., James, Eddie A., Kent, Sally C., Speake, Cate, Homann, Dirk, and Long, S. Alice

Subjects
TYPE 1 diabetes, T cells, CYTOMETRY, BIOMARKERS, CELL populations
Abstract

Cytometric immunophenotyping is a powerful tool to discover and implement T‐cell biomarkers of type 1 diabetes (T1D) progression and response to clinical therapy. Although many discovery‐based T‐cell biomarkers have been described, to date, no such markers have been widely adopted in standard practice. The heterogeneous nature of T1D and lack of standardized assays and experimental design across studies is a major barrier to the broader adoption of T‐cell immunophenotyping assays. There is an unmet need to harmonize the design of immunophenotyping assays, including those that measure antigen‐agnostic cell populations, such that data collected from different clinical trial sites and T1D cohorts are comparable, yet account for cohort‐specific features and different drug mechanisms of action. In these Guidelines, we aim to provide expert advice on how to unify aspects of study design and practice. We provide recommendations for defining cohorts, method implementation, as well as tools for data analysis and reporting by highlighting and building on selected successes. Harmonization of cytometry‐based T‐cell assays will allow researchers to better integrate findings across trials, ultimately enabling the identification and validation of biomarkers of disease progression and treatment response in T1D. [ABSTRACT FROM AUTHOR]

Published
2022
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9. Helios is a marker, not a driver, of human Treg stability.

Author

Lam, Avery J., Uday, Prakruti, Gillies, Jana K., and Levings, Megan K.

Subjects
REGULATORY T cells, IMMUNOLOGICAL tolerance, T cells, TRANSCRIPTION factors, IMMUNE response
Abstract

Treg therapy holds promise as a potentially curative approach to establish immune tolerance in transplantation and autoimmune disease. An outstanding question is whether therapeutic Tregs have the potential to transdifferentiate into effector T‐cells and, thus, exacerbate rather than suppress immune responses. In mice, the transcription factor Helios is thought to promote Treg lineage stability in a range of inflammatory contexts. In humans, the role of Helios in Tregs is less clear, in part, due to the inability to enrich and study subsets of Helios‐positive versus Helios‐negative Tregs. Using an in vitro expansion system, we found that loss of high Helios expression and emergence of an intermediate Helios (Heliosmid)‐expressing population correlated with Treg destabilization. We used CRISPR/Cas9 to genetically ablate Helios expression in human naive or memory Tregs and found that Helios‐KO and unedited Tregs were equivalent in their suppressive function and stability in inflammation. Thus, high Helios expression is a marker, but not a driver, of human Treg stability in vitro. These data highlight the importance of monitoring Helios expression in therapeutic Treg manufacturing and provide new insight into the biological function of this transcription factor in human T‐cells. [ABSTRACT FROM AUTHOR]

Published
2022
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11. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author

Cossarizza, Andrea, primary, Chang, Hyun‐Dong, additional, Radbruch, Andreas, additional, Acs, Andreas, additional, Adam, Dieter, additional, Adam‐Klages, Sabine, additional, Agace, William W., additional, Aghaeepour, Nima, additional, Akdis, Mübeccel, additional, Allez, Matthieu, additional, Almeida, Larissa Nogueira, additional, Alvisi, Giorgia, additional, Anderson, Graham, additional, Andrä, Immanuel, additional, Annunziato, Francesco, additional, Anselmo, Achille, additional, Bacher, Petra, additional, Baldari, Cosima T., additional, Bari, Sudipto, additional, Barnaba, Vincenzo, additional, Barros‐Martins, Joana, additional, Battistini, Luca, additional, Bauer, Wolfgang, additional, Baumgart, Sabine, additional, Baumgarth, Nicole, additional, Baumjohann, Dirk, additional, Baying, Bianka, additional, Bebawy, Mary, additional, Becher, Burkhard, additional, Beisker, Wolfgang, additional, Benes, Vladimir, additional, Beyaert, Rudi, additional, Blanco, Alfonso, additional, Boardman, Dominic A., additional, Bogdan, Christian, additional, Borger, Jessica G., additional, Borsellino, Giovanna, additional, Boulais, Philip E., additional, Bradford, Jolene A., additional, Brenner, Dirk, additional, Brinkman, Ryan R., additional, Brooks, Anna E. S., additional, Busch, Dirk H., additional, Büscher, Martin, additional, Bushnell, Timothy P., additional, Calzetti, Federica, additional, Cameron, Garth, additional, Cammarata, Ilenia, additional, Cao, Xuetao, additional, Cardell, Susanna L., additional, Casola, Stefano, additional, Cassatella, Marco A., additional, Cavani, Andrea, additional, Celada, Antonio, additional, Chatenoud, Lucienne, additional, Chattopadhyay, Pratip K., additional, Chow, Sue, additional, Christakou, Eleni, additional, Čičin‐Šain, Luka, additional, Clerici, Mario, additional, Colombo, Federico S., additional, Cook, Laura, additional, Cooke, Anne, additional, Cooper, Andrea M., additional, Corbett, Alexandra J., additional, Cosma, Antonio, additional, Cosmi, Lorenzo, additional, Coulie, Pierre G., additional, Cumano, Ana, additional, Cvetkovic, Ljiljana, additional, Dang, Van Duc, additional, Dang‐Heine, Chantip, additional, Davey, Martin S., additional, Davies, Derek, additional, De Biasi, Sara, additional, Del Zotto, Genny, additional, Dela Cruz, Gelo Victoriano, additional, Delacher, Michael, additional, Della Bella, Silvia, additional, Dellabona, Paolo, additional, Deniz, Günnur, additional, Dessing, Mark, additional, Di Santo, James P., additional, Diefenbach, Andreas, additional, Dieli, Francesco, additional, Dolf, Andreas, additional, Dörner, Thomas, additional, Dress, Regine J., additional, Dudziak, Diana, additional, Dustin, Michael, additional, Dutertre, Charles‐Antoine, additional, Ebner, Friederike, additional, Eckle, Sidonia B. G., additional, Edinger, Matthias, additional, Eede, Pascale, additional, Ehrhardt, Götz R.A., additional, Eich, Marcus, additional, Engel, Pablo, additional, Engelhardt, Britta, additional, Erdei, Anna, additional, Esser, Charlotte, additional, Everts, Bart, additional, Evrard, Maximilien, additional, Falk, Christine S., additional, Fehniger, Todd A., additional, Felipo‐Benavent, Mar, additional, Ferry, Helen, additional, Feuerer, Markus, additional, Filby, Andrew, additional, Filkor, Kata, additional, Fillatreau, Simon, additional, Follo, Marie, additional, Förster, Irmgard, additional, Foster, John, additional, Foulds, Gemma A., additional, Frehse, Britta, additional, Frenette, Paul S., additional, Frischbutter, Stefan, additional, Fritzsche, Wolfgang, additional, Galbraith, David W., additional, Gangaev, Anastasia, additional, Garbi, Natalio, additional, Gaudilliere, Brice, additional, Gazzinelli, Ricardo T., additional, Geginat, Jens, additional, Gerner, Wilhelm, additional, Gherardin, Nicholas A., additional, Ghoreschi, Kamran, additional, Gibellini, Lara, additional, Ginhoux, Florent, additional, Goda, Keisuke, additional, Godfrey, Dale I., additional, Goettlinger, Christoph, additional, González‐Navajas, Jose M., additional, Goodyear, Carl S., additional, Gori, Andrea, additional, Grogan, Jane L., additional, Grummitt, Daryl, additional, Grützkau, Andreas, additional, Haftmann, Claudia, additional, Hahn, Jonas, additional, Hammad, Hamida, additional, Hämmerling, Günter, additional, Hansmann, Leo, additional, Hansson, Goran, additional, Harpur, Christopher M., additional, Hartmann, Susanne, additional, Hauser, Andrea, additional, Hauser, Anja E., additional, Haviland, David L., additional, Hedley, David, additional, Hernández, Daniela C., additional, Herrera, Guadalupe, additional, Herrmann, Martin, additional, Hess, Christoph, additional, Höfer, Thomas, additional, Hoffmann, Petra, additional, Hogquist, Kristin, additional, Holland, Tristan, additional, Höllt, Thomas, additional, Holmdahl, Rikard, additional, Hombrink, Pleun, additional, Houston, Jessica P., additional, Hoyer, Bimba F., additional, Huang, Bo, additional, Huang, Fang‐Ping, additional, Huber, Johanna E., additional, Huehn, Jochen, additional, Hundemer, Michael, additional, Hunter, Christopher A., additional, Hwang, William Y. K., additional, Iannone, Anna, additional, Ingelfinger, Florian, additional, Ivison, Sabine M, additional, Jäck, Hans‐Martin, additional, Jani, Peter K., additional, Jávega, Beatriz, additional, Jonjic, Stipan, additional, Kaiser, Toralf, additional, Kalina, Tomas, additional, Kamradt, Thomas, additional, Kaufmann, Stefan H. E., additional, Keller, Baerbel, additional, Ketelaars, Steven L. C., additional, Khalilnezhad, Ahad, additional, Khan, Srijit, additional, Kisielow, Jan, additional, Klenerman, Paul, additional, Knopf, Jasmin, additional, Koay, Hui‐Fern, additional, Kobow, Katja, additional, Kolls, Jay K., additional, Kong, Wan Ting, additional, Kopf, Manfred, additional, Korn, Thomas, additional, Kriegsmann, Katharina, additional, Kristyanto, Hendy, additional, Kroneis, Thomas, additional, Krueger, Andreas, additional, Kühne, Jenny, additional, Kukat, Christian, additional, Kunkel, Désirée, additional, Kunze‐Schumacher, Heike, additional, Kurosaki, Tomohiro, additional, Kurts, Christian, additional, Kvistborg, Pia, additional, Kwok, Immanuel, additional, Landry, Jonathan, additional, Lantz, Olivier, additional, Lanuti, Paola, additional, LaRosa, Francesca, additional, Lehuen, Agnès, additional, LeibundGut‐Landmann, Salomé, additional, Leipold, Michael D., additional, Leung, Leslie Y.T., additional, Levings, Megan K., additional, Lino, Andreia C., additional, Liotta, Francesco, additional, Litwin, Virginia, additional, Liu, Yanling, additional, Ljunggren, Hans‐Gustaf, additional, Lohoff, Michael, additional, Lombardi, Giovanna, additional, Lopez, Lilly, additional, López‐Botet, Miguel, additional, Lovett‐Racke, Amy E., additional, Lubberts, Erik, additional, Luche, Herve, additional, Ludewig, Burkhard, additional, Lugli, Enrico, additional, Lunemann, Sebastian, additional, Maecker, Holden T., additional, Maggi, Laura, additional, Maguire, Orla, additional, Mair, Florian, additional, Mair, Kerstin H., additional, Mantovani, Alberto, additional, Manz, Rudolf A., additional, Marshall, Aaron J., additional, Martínez‐Romero, Alicia, additional, Martrus, Glòria, additional, Marventano, Ivana, additional, Maslinski, Wlodzimierz, additional, Matarese, Giuseppe, additional, Mattioli, Anna Vittoria, additional, Maueröder, Christian, additional, Mazzoni, Alessio, additional, McCluskey, James, additional, McGrath, Mairi, additional, McGuire, Helen M., additional, McInnes, Iain B., additional, Mei, Henrik E., additional, Melchers, Fritz, additional, Melzer, Susanne, additional, Mielenz, Dirk, additional, Miller, Stephen D., additional, Mills, Kingston H.G., additional, Minderman, Hans, additional, Mjösberg, Jenny, additional, Moore, Jonni, additional, Moran, Barry, additional, Moretta, Lorenzo, additional, Mosmann, Tim R., additional, Müller, Susann, additional, Multhoff, Gabriele, additional, Muñoz, Luis Enrique, additional, Münz, Christian, additional, Nakayama, Toshinori, additional, Nasi, Milena, additional, Neumann, Katrin, additional, Ng, Lai Guan, additional, Niedobitek, Antonia, additional, Nourshargh, Sussan, additional, Núñez, Gabriel, additional, O'Connor, José‐Enrique, additional, Ochel, Aaron, additional, Oja, Anna, additional, Ordonez, Diana, additional, Orfao, Alberto, additional, Orlowski‐Oliver, Eva, additional, Ouyang, Wenjun, additional, Oxenius, Annette, additional, Palankar, Raghavendra, additional, Panse, Isabel, additional, Pattanapanyasat, Kovit, additional, Paulsen, Malte, additional, Pavlinic, Dinko, additional, Penter, Livius, additional, Peterson, Pärt, additional, Peth, Christian, additional, Petriz, Jordi, additional, Piancone, Federica, additional, Pickl, Winfried F., additional, Piconese, Silvia, additional, Pinti, Marcello, additional, Pockley, A. Graham, additional, Podolska, Malgorzata Justyna, additional, Poon, Zhiyong, additional, Pracht, Katharina, additional, Prinz, Immo, additional, Pucillo, Carlo E. M., additional, Quataert, Sally A., additional, Quatrini, Linda, additional, Quinn, Kylie M., additional, Radbruch, Helena, additional, Radstake, Tim R. D. J., additional, Rahmig, Susann, additional, Rahn, Hans‐Peter, additional, Rajwa, Bartek, additional, Ravichandran, Gevitha, additional, Raz, Yotam, additional, Rebhahn, Jonathan A., additional, Recktenwald, Diether, additional, Reimer, Dorothea, additional, Reis e Sousa, Caetano, additional, Remmerswaal, Ester B.M., additional, Richter, Lisa, additional, Rico, Laura G., additional, Riddell, Andy, additional, Rieger, Aja M., additional, Robinson, J. Paul, additional, Romagnani, Chiara, additional, Rubartelli, Anna, additional, Ruland, Jürgen, additional, Saalmüller, Armin, additional, Saeys, Yvan, additional, Saito, Takashi, additional, Sakaguchi, Shimon, additional, Sala‐de‐Oyanguren, Francisco, additional, Samstag, Yvonne, additional, Sanderson, Sharon, additional, Sandrock, Inga, additional, Santoni, Angela, additional, Sanz, Ramon Bellmàs, additional, Saresella, Marina, additional, Sautes‐Fridman, Catherine, additional, Sawitzki, Birgit, additional, Schadt, Linda, additional, Scheffold, Alexander, additional, Scherer, Hans U., additional, Schiemann, Matthias, additional, Schildberg, Frank A., additional, Schimisky, Esther, additional, Schlitzer, Andreas, additional, Schlosser, Josephine, additional, Schmid, Stephan, additional, Schmitt, Steffen, additional, Schober, Kilian, additional, Schraivogel, Daniel, additional, Schuh, Wolfgang, additional, Schüler, Thomas, additional, Schulte, Reiner, additional, Schulz, Axel Ronald, additional, Schulz, Sebastian R., additional, Scottá, Cristiano, additional, Scott‐Algara, Daniel, additional, Sester, David P., additional, Shankey, T. Vincent, additional, Silva‐Santos, Bruno, additional, Simon, Anna Katharina, additional, Sitnik, Katarzyna M., additional, Sozzani, Silvano, additional, Speiser, Daniel E., additional, Spidlen, Josef, additional, Stahlberg, Anders, additional, Stall, Alan M., additional, Stanley, Natalie, additional, Stark, Regina, additional, Stehle, Christina, additional, Steinmetz, Tobit, additional, Stockinger, Hannes, additional, Takahama, Yousuke, additional, Takeda, Kiyoshi, additional, Tan, Leonard, additional, Tárnok, Attila, additional, Tiegs, Gisa, additional, Toldi, Gergely, additional, Tornack, Julia, additional, Traggiai, Elisabetta, additional, Trebak, Mohamed, additional, Tree, Timothy I.M., additional, Trotter, Joe, additional, Trowsdale, John, additional, Tsoumakidou, Maria, additional, Ulrich, Henning, additional, Urbanczyk, Sophia, additional, van de Veen, Willem, additional, van den Broek, Maries, additional, van der Pol, Edwin, additional, Van Gassen, Sofie, additional, Van Isterdael, Gert, additional, van Lier, René A.W., additional, Veldhoen, Marc, additional, Vento‐Asturias, Salvador, additional, Vieira, Paulo, additional, Voehringer, David, additional, Volk, Hans‐Dieter, additional, von Borstel, Anouk, additional, von Volkmann, Konrad, additional, Waisman, Ari, additional, Walker, Rachael V., additional, Wallace, Paul K., additional, Wang, Sa A., additional, Wang, Xin M., additional, Ward, Michael D., additional, Ward‐Hartstonge, Kirsten A, additional, Warnatz, Klaus, additional, Warnes, Gary, additional, Warth, Sarah, additional, Waskow, Claudia, additional, Watson, James V., additional, Watzl, Carsten, additional, Wegener, Leonie, additional, Weisenburger, Thomas, additional, Wiedemann, Annika, additional, Wienands, Jürgen, additional, Wilharm, Anneke, additional, Wilkinson, Robert John, additional, Willimsky, Gerald, additional, Wing, James B., additional, Winkelmann, Rieke, additional, Winkler, Thomas H., additional, Wirz, Oliver F., additional, Wong, Alicia, additional, Wurst, Peter, additional, Yang, Jennie H. M., additional, Yang, Juhao, additional, Yazdanbakhsh, Maria, additional, Yu, Liping, additional, Yue, Alice, additional, Zhang, Hanlin, additional, Zhao, Yi, additional, Ziegler, Susanne Maria, additional, Zielinski, Christina, additional, Zimmermann, Jakob, additional, and Zychlinsky, Arturo, additional

Published
2019
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12. Characterization of regulatory T cells in obese omental adipose tissue in humans

Author

Wu, Dan, primary, Han, Jonathan M., additional, Yu, Xin, additional, Lam, Avery J., additional, Hoeppli, Romy E., additional, Pesenacker, Anne M., additional, Huang, Qing, additional, Chen, Virginia, additional, Speake, Cate, additional, Yorke, Ekua, additional, Nguyen, Nam, additional, Sampath, Sharadh, additional, Harris, David, additional, and Levings, Megan K., additional

Published
2019
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13. Cross talk between human regulatory T cells and antigen‐presenting cells: Lessons for clinical applications.

Author

Wardell, Christine M, MacDonald, Katherine N, Levings, Megan K, and Cook, Laura

Subjects
SUPPRESSOR cells, CROSSTALK, INFLAMMATORY bowel diseases, HUMAN biology, TYPE 1 diabetes
Abstract

Regulatory T cells (Tregs) have a critical role in maintaining self‐tolerance and immune homeostasis. There is much interest in using Tregs as a cell therapy to re‐establish tolerance in conditions such as inflammatory bowel disease and type 1 diabetes, with many ongoing clinical studies testing the safety and efficacy of this approach. Manufacturing of Tregs for therapy typically involves ex vivo expansion to obtain sufficient cell numbers for infusion and comes with the risk of altering the activity of key biological processes. However, this process also offers an opportunity to tailor Treg function to maximize in vivo activity. In this review, we focus on the roles of antigen‐presenting cells (APCs) in the generation and function of Tregs in humans. In addition to stimulating the development of Tregs, APCs activate Tregs and provide signals that induce specialized functional and homing marker expression. Cross talk between Tregs and APCs is a critical, often under‐appreciated, aspect of Treg biology, with APCs mediating the key properties of infectious tolerance and bystander suppression. Understanding the biology of human Treg‐APC interactions will reveal new ways to optimize Treg‐based therapeutic approaches. [ABSTRACT FROM AUTHOR]

Published
2021
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15. Guidelines for the use of flow cytometry and cell sorting in immunological studies *

Author

Cossarizza, Andrea, primary, Chang, Hyun‐Dong, additional, Radbruch, Andreas, additional, Akdis, Mübeccel, additional, Andrä, Immanuel, additional, Annunziato, Francesco, additional, Bacher, Petra, additional, Barnaba, Vincenzo, additional, Battistini, Luca, additional, Bauer, Wolfgang M., additional, Baumgart, Sabine, additional, Becher, Burkhard, additional, Beisker, Wolfgang, additional, Berek, Claudia, additional, Blanco, Alfonso, additional, Borsellino, Giovanna, additional, Boulais, Philip E., additional, Brinkman, Ryan R., additional, Büscher, Martin, additional, Busch, Dirk H., additional, Bushnell, Timothy P., additional, Cao, Xuetao, additional, Cavani, Andrea, additional, Chattopadhyay, Pratip K., additional, Cheng, Qingyu, additional, Chow, Sue, additional, Clerici, Mario, additional, Cooke, Anne, additional, Cosma, Antonio, additional, Cosmi, Lorenzo, additional, Cumano, Ana, additional, Dang, Van Duc, additional, Davies, Derek, additional, Biasi, Sara, additional, Del Zotto, Genny, additional, Della Bella, Silvia, additional, Dellabona, Paolo, additional, Deniz, Günnur, additional, Dessing, Mark, additional, Diefenbach, Andreas, additional, Di Santo, James, additional, Dieli, Francesco, additional, Dolf, Andreas, additional, Donnenberg, Vera S., additional, Dörner, Thomas, additional, Ehrhardt, Götz R. A., additional, Endl, Elmar, additional, Engel, Pablo, additional, Engelhardt, Britta, additional, Esser, Charlotte, additional, Everts, Bart, additional, Dreher, Anita, additional, Falk, Christine S., additional, Fehniger, Todd A., additional, Filby, Andrew, additional, Fillatreau, Simon, additional, Follo, Marie, additional, Förster, Irmgard, additional, Foster, John, additional, Foulds, Gemma A., additional, Frenette, Paul S., additional, Galbraith, David, additional, Garbi, Natalio, additional, García‐Godoy, Maria Dolores, additional, Geginat, Jens, additional, Ghoreschi, Kamran, additional, Gibellini, Lara, additional, Goettlinger, Christoph, additional, Goodyear, Carl S., additional, Gori, Andrea, additional, Grogan, Jane, additional, Gross, Mor, additional, Grützkau, Andreas, additional, Grummitt, Daryl, additional, Hahn, Jonas, additional, Hammer, Quirin, additional, Hauser, Anja E., additional, Haviland, David L., additional, Hedley, David, additional, Herrera, Guadalupe, additional, Herrmann, Martin, additional, Hiepe, Falk, additional, Holland, Tristan, additional, Hombrink, Pleun, additional, Houston, Jessica P., additional, Hoyer, Bimba F., additional, Huang, Bo, additional, Hunter, Christopher A., additional, Iannone, Anna, additional, Jäck, Hans‐Martin, additional, Jávega, Beatriz, additional, Jonjic, Stipan, additional, Juelke, Kerstin, additional, Jung, Steffen, additional, Kaiser, Toralf, additional, Kalina, Tomas, additional, Keller, Baerbel, additional, Khan, Srijit, additional, Kienhöfer, Deborah, additional, Kroneis, Thomas, additional, Kunkel, Désirée, additional, Kurts, Christian, additional, Kvistborg, Pia, additional, Lannigan, Joanne, additional, Lantz, Olivier, additional, Larbi, Anis, additional, LeibundGut‐Landmann, Salome, additional, Leipold, Michael D., additional, Levings, Megan K., additional, Litwin, Virginia, additional, Liu, Yanling, additional, Lohoff, Michael, additional, Lombardi, Giovanna, additional, Lopez, Lilly, additional, Lovett‐Racke, Amy, additional, Lubberts, Erik, additional, Ludewig, Burkhard, additional, Lugli, Enrico, additional, Maecker, Holden T., additional, Martrus, Glòria, additional, Matarese, Giuseppe, additional, Maueröder, Christian, additional, McGrath, Mairi, additional, McInnes, Iain, additional, Mei, Henrik E., additional, Melchers, Fritz, additional, Melzer, Susanne, additional, Mielenz, Dirk, additional, Mills, Kingston, additional, Mirrer, David, additional, Mjösberg, Jenny, additional, Moore, Jonni, additional, Moran, Barry, additional, Moretta, Alessandro, additional, Moretta, Lorenzo, additional, Mosmann, Tim R., additional, Müller, Susann, additional, Müller, Werner, additional, Münz, Christian, additional, Multhoff, Gabriele, additional, Munoz, Luis Enrique, additional, Murphy, Kenneth M., additional, Nakayama, Toshinori, additional, Nasi, Milena, additional, Neudörfl, Christine, additional, Nolan, John, additional, Nourshargh, Sussan, additional, O'Connor, José‐Enrique, additional, Ouyang, Wenjun, additional, Oxenius, Annette, additional, Palankar, Raghav, additional, Panse, Isabel, additional, Peterson, Pärt, additional, Peth, Christian, additional, Petriz, Jordi, additional, Philips, Daisy, additional, Pickl, Winfried, additional, Piconese, Silvia, additional, Pinti, Marcello, additional, Pockley, A. Graham, additional, Podolska, Malgorzata Justyna, additional, Pucillo, Carlo, additional, Quataert, Sally A., additional, Radstake, Timothy R. D. J., additional, Rajwa, Bartek, additional, Rebhahn, Jonathan A., additional, Recktenwald, Diether, additional, Remmerswaal, Ester B.M., additional, Rezvani, Katy, additional, Rico, Laura G., additional, Robinson, J. Paul, additional, Romagnani, Chiara, additional, Rubartelli, Anna, additional, Ruckert, Beate, additional, Ruland, Jürgen, additional, Sakaguchi, Shimon, additional, Sala‐de‐Oyanguren, Francisco, additional, Samstag, Yvonne, additional, Sanderson, Sharon, additional, Sawitzki, Birgit, additional, Scheffold, Alexander, additional, Schiemann, Matthias, additional, Schildberg, Frank, additional, Schimisky, Esther, additional, Schmid, Stephan A, additional, Schmitt, Steffen, additional, Schober, Kilian, additional, Schüler, Thomas, additional, Schulz, Axel Ronald, additional, Schumacher, Ton, additional, Scotta, Cristiano, additional, Shankey, T. Vincent, additional, Shemer, Anat, additional, Simon, Anna‐Katharina, additional, Spidlen, Josef, additional, Stall, Alan M., additional, Stark, Regina, additional, Stehle, Christina, additional, Stein, Merle, additional, Steinmetz, Tobit, additional, Stockinger, Hannes, additional, Takahama, Yousuke, additional, Tarnok, Attila, additional, Tian, ZhiGang, additional, Toldi, Gergely, additional, Tornack, Julia, additional, Traggiai, Elisabetta, additional, Trotter, Joe, additional, Ulrich, Henning, additional, der Braber, Marlous, additional, Lier, René A. W., additional, Veldhoen, Marc, additional, Vento‐Asturias, Salvador, additional, Vieira, Paulo, additional, Voehringer, David, additional, Volk, Hans‐Dieter, additional, Volkmann, Konrad, additional, Waisman, Ari, additional, Walker, Rachael, additional, Ward, Michael D., additional, Warnatz, Klaus, additional, Warth, Sarah, additional, Watson, James V., additional, Watzl, Carsten, additional, Wegener, Leonie, additional, Wiedemann, Annika, additional, Wienands, Jürgen, additional, Willimsky, Gerald, additional, Wing, James, additional, Wurst, Peter, additional, Yu, Liping, additional, Yue, Alice, additional, Zhang, Qianjun, additional, Zhao, Yi, additional, Ziegler, Susanne, additional, and Zimmermann, Jakob, additional

Published
2017
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23. CD161 is a marker of all human IL-17-producing T-cell subsets and is induced by RORC

Author

Maggi, Laura, primary, Santarlasci, Veronica, additional, Capone, Manuela, additional, Peired, Anna, additional, Frosali, Francesca, additional, Crome, Sarah Q., additional, Querci, Valentina, additional, Fambrini, Massimiliano, additional, Liotta, Francesco, additional, Levings, Megan K., additional, Maggi, Enrico, additional, Cosmi, Lorenzo, additional, Romagnani, Sergio, additional, and Annunziato, Francesco, additional

Published
2010
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26. Control of tissue-localized immune responses by human regulatory T cells.

Author

Pesenacker, Anne M., Broady, Raewyn, and Levings, Megan K.

Abstract

Treg cells control immune responses to self and nonharmful foreign antigens. Emerging data from animal models indicate that Treg cells function in both secondary lymphoid organs and tissues, and that these different microenvironments may contain specialized subsets of Treg cells with distinct mechanisms of action. The design of therapies for the restoration of tissue-localized immune homeostasis is dependent upon understanding how local immune responses are influenced by Treg cells in health versus disease. Here we review the current state of knowledge about human Treg cells in four locations: the skin, lung, intestine, and joint. Despite the distinct biology of these tissues, there are commonalities in the biology of their resident Treg cells, including phenotypic and functional differences from circulating Treg cells, and the presence of cytokine-producing (e.g. IL-17+) FOXP3+ cells. We also highlight the challenges to studying tissue Treg cells in humans, and opportunities to use new technologies for the detailed analysis of Treg cells at the single-cell level. As emerging biological therapies are increasingly targeted toward tissue-specific effects, it is critical to understand their potential impact on local immune regulation. [ABSTRACT FROM AUTHOR]

Published
2015
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27. Suppression assays with human T regulatory cells: A technical guide.

Author

McMurchy, Alicia N. and Levings, Megan K.

Abstract

The suppression of inappropriate immune responses by Treg cells is one of the major ways that the body maintains immune tolerance and homeostasis. Since defects in the suppressive capacity of Treg cells underlie many different immune-mediated diseases, there is great interest in developing ways to track the number and function of Treg cells as biomarkers of tolerance and in devising ways to enhance their function therapeutically. However, the methods of studying human Treg cells are fraught with technical challenges that can often lead to misinterpretation. The most common way to determine the suppressive capacity of human Treg cells is to measure their ability to suppress the proliferation of responding CD4+ T cells. Here, we discuss the technical considerations that must be taken into account when performing suppression of T-cell proliferation assays with human Treg cells. We also consider how T cells may falsely appear suppressive because of dying cells in the system, improper resting of T-cell lines prior to the assay, or insufficient proliferation of the responding T cells. We propose that, in the future, classification of a population of cells as 'regulatory' should rely on more than a simple test for blockade of CD4+ T-cell proliferation. [ABSTRACT FROM AUTHOR]

Published
2012
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28. CD4+Foxp3+ regulatory T cells suppress γδ T-cell effector functions in a model of T-cell-induced mucosal inflammation.

Author

Yurchenko, Ekaterina, Levings, Megan K., and Piccirillo, Ciriaco A.

Abstract

CD4+CD25+Foxp3+ regulatory T (TREG) cells are critical mediators of peripheral immune tolerance, and abrogation of their function provokes a variety of autoimmune and inflammatory states including inflammatory bowel disease. In this study, we investigate the functional dynamics of TREG-cell responses in a CD4+ T-cell-induced model of intestinal inflammation in αβ T-cell-deficient (TCR-β−/−) hosts to gain insights into the mechanism and cellular targets of suppression in vivo. We show that CD4+ T effector cell transfer into T-cell-deficient mice rapidly induces mucosal inflammation and colitis development, which is associated with prominent Th1 and Th17 responses. Interestingly, we unveil a prominent role for resident γδ T cells in mucosal inflammation as they promote Th1 and particularly Th17 responses in the early phase of inflammation, thus exacerbating colitis development. We further demonstrate that CD4+CD25+Foxp3+ TREG cells readily inhibit these responses and mediate disease protection, which correlates with their accumulation in the draining LN and lamina propria. Moreover, TREG cells can directly suppress γδ T-cell expansion and cytokine production in vitro and in vivo, suggesting a pathogenic role of γδ T cells in intestinal inflammation. Thus, functional alterations in TREG cells provoke dysregulated CD4+ and γδ T-cell responses to commensal antigens in the intestine. [ABSTRACT FROM AUTHOR]

Published
2011
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29. Human CD4.

Author

Himmel, Megan E., Crome, Sarah Q., Ivison, Sabine, Piccirillo, Ciriaco, Steiner, Theodore S., and Levings, Megan K.

Published
2011
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31. Guidelines for the use of flow cytometry and cell sorting in immunological studies

Author

Guadalupe Herrera, Jens Geginat, Daryl Grummitt, Vincenzo Barnaba, Joanne Lannigan, Beate Rückert, Elisabetta Traggiai, Christian Münz, Susanne Melzer, Ari Waisman, Pratip K. Chattopadhyay, Jonas Hahn, T. Vincent Shankey, S Schmid, Julia Tornack, David W. Hedley, Paolo Dellabona, Jürgen Wienands, Ana Cumano, Ester B. M. Remmerswaal, Christopher A. Hunter, Van Duc Dang, Anis Larbi, Timothy P. Bushnell, Mor Gross, Wenjun Ouyang, Vera S. Donnenberg, Lilly Lopez, Holden T. Maecker, Jenny Mjösberg, Christina Stehle, Yanling Liu, Alan M. Stall, Anja E. Hauser, Yousuke Takahama, Mark C. Dessing, Gergely Toldi, Klaus Warnatz, Raghav Palankar, Sussan Nourshargh, Enrico Lugli, Bimba F. Hoyer, Pleun Hombrink, Bartek Rajwa, Sarah Warth, Isabel Panse, Rachael C. Walker, Silvia Piconese, Andrew Filby, Pärt Peterson, Kilian Schober, Silvia Della Bella, Leonie Wegener, Merle Stein, Anne Cooke, Alessandro Moretta, Deborah Kienhöfer, Andrea Cossarizza, Hyun-Dong Chang, Konrad von Volkmann, Jessica P. Houston, Mübeccel Akdis, Andreas Grützkau, Tristan Holland, Jakob Zimmermann, Jonni S. Moore, Dirk Mielenz, Iain B. McInnes, Bo Huang, Paulo Vieira, Thomas Kroneis, Tobit Steinmetz, Kerstin Juelke, Sharon Sanderson, James V. Watson, Srijit Khan, Sally A. Quataert, Winfried F. Pickl, Annika Wiedemann, Sara De Biasi, Andreas Radbruch, James B. Wing, Susann Müller, Ton N. Schumacher, Katy Rezvani, Gloria Martrus, Alexander Scheffold, Toralf Kaiser, Carlo Pucillo, Lara Gibellini, Anna Rubartelli, Qingyu Cheng, Luca Battistini, David Mirrer, David W. Galbraith, Giovanna Borsellino, Ryan R. Brinkman, Tim R. Mosmann, Laura G. Rico, Anita Dreher, Désirée Kunkel, Francesco Annunziato, Pia Kvistborg, Andrea Gori, Chiara Romagnani, Anat Shemer, Toshinori Nakayama, Francisco Sala-de-Oyanguren, Attila Tárnok, Alfonso Blanco, Anna Iannone, Giuseppe Matarese, Thomas Dörner, Virginia Litwin, Michael Lohoff, Petra Bacher, Jordi Petriz, Lorenzo Moretta, Götz R. A. Ehrhardt, Qianjun Zhang, Andrea Cavani, Barry Moran, Christian Maueröder, Immanuel Andrä, Dirk H. Busch, Joe Trotter, Timothy R D J Radstake, Stipan Jonjić, Fritz Melchers, Hans-Martin Jäck, Beatriz Jávega, Gerald Willimsky, Martin Büscher, Henrik E. Mei, Christine S. Falk, Zhigang Tian, Martin Herrmann, Alice Yue, Steffen Jung, Bart Everts, Frank A. Schildberg, John Bellamy Foster, Giovanna Lombardi, Milena Nasi, John P. Nolan, Todd A. Fehniger, Francesco Dieli, Steffen Schmitt, Andreas Dolf, A. Graham Pockley, Claudia Berek, Josef Spidlen, Megan K. Levings, Werner Müller, Baerbel Keller, René A. W. van Lier, Daisy Philips, Susanne Ziegler, Christian Kurts, Malgorzata J. Podolska, Jürgen Ruland, David Voehringer, Kenneth M. Murphy, Marlous van der Braber, Maria Dolores García-Godoy, Sabine Baumgart, Yi Zhao, Antonio Cosma, Falk Hiepe, Charlotte Esser, Pablo Engel, Marcello Veldhoen, Irmgard Förster, Amy E. Lovett-Racke, Günnur Deniz, Burkhard Ludewig, Esther Schimisky, Cristiano Scottà, Marcello Pinti, Jonathan Rebhahn, Regina Stark, Mario Clerici, Liping Yu, Shimon Sakaguchi, Derek Davies, Anna Katharina Simon, Lorenzo Cosmi, Gabriele Multhoff, Kamran Ghoreschi, Quirin Hammer, Henning Ulrich, J. Paul Robinson, Yvonne Samstag, Olivier Lantz, Hannes Stockinger, Xuetao Cao, Simon Fillatreau, David L. Haviland, Natalio Garbi, C. Neudörfl, Kingston H. G. Mills, Salvador Vento-Asturias, Christian Peth, Philip E. Boulais, Diether J. Recktenwald, Burkhard Becher, Tomas Kalina, Michael D. Leipold, Christoph Goettlinger, Gemma A. Foulds, Jane L. Grogan, Axel R. Schulz, James P. Di Santo, Matthias Schiemann, Michael D. Ward, Britta Engelhardt, Birgit Sawitzki, Annette Oxenius, Carl S. Goodyear, Salomé LeibundGut-Landmann, Wolfgang Beisker, Sue Chow, Carsten Watzl, Marie Follo, Erik Lubberts, Peter Wurst, Thomas Schüler, Andreas Diefenbach, Wolfgang Bauer, Hans-Dieter Volk, Luis E. Muñoz, Elmar Endl, Genny Del Zotto, José-Enrique O'Connor, Mairi McGrath, Paul S. Frenette, Dipartimento di Scienze Biomediche, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Cell Biology, Klinik für Dermatologie, Venerologie und Allergologie, Department of Internal Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-DENOTHE Center, Neuroimmunology Unit, Santa Lucia Foundation (IRCCS), Inorganic Chemistry II, Universität Bayreuth, Caprotec Bioanalytics GmbH, International Occultation Timing Association European Section (IOTA ES), International Occultation Timing Association European Section, Institut der Leibniz-Gemeinschaft, Berlin, Fondazione Santa Lucia (IRCCS), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, Department of Immunology, Chinese Academy of Medical Sciences, Fondazione Don Carlo Gnocchi, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Experimental Immunology Unit, Dept. of Oncology, DIBIT San Raffaele Scientific Institute, Département d'Immunologie - Department of Immunology, Institut Pasteur [Paris], Charité Hospital, Humboldt-Universität zu Berlin, Universitat de Barcelona (UB), Rheumatologie, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Department of Histology and Embryology, University of Rijeka, Weizmann Institute of Science [Rehovot, Israël], Régulation des Infections Rétrovirales, Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Institute of Virology [Zürich], College of Food Science and Technology [Shangai], Shanghai Ocean University, Institute for Medical Microbiology and Hygiene, University of Marburg, Centre for Transplantation, King's College London (MRC), Guy's Hospital [London], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Institute, Heinrich Pette Institute [Hamburg], Institute of Translational Medicine, Department of Medicine Huddinge, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Lipid Laboratory, Università di Genova, Dipartimento di Medicina Sperimentale, Department of Environmental Microbiology, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Experimental Immunology, Helmholtz Centre for Infection Research (HZI), Viral Immunobiology, Universität Zürich [Zürich] = University of Zurich (UZH)-Institute of Experimental Immunology [Zurich], Department of Radiation Oncology [Munich], Ludwig-Maximilians-Universität München (LMU), Department of Mathematics and Statistics, American University, William Harvey Research Institute, Barts and the London Medical School, Cytometry Laboratories and School of Veterinary Medicine, Purdue University [West Lafayette], Osaka University [Osaka], FACS and Array Core Facility, Johannes Gutenberg - Universität Mainz (JGU), Institute for Cognitive Science, University of Osnabrueck, Department of Molecular Immunology, Medizinische Universität Wien = Medical University of Vienna, Universität Leipzig [Leipzig], Institute of Immunology, School of Life Sciences-University of Science & Technology of China [Suzhou], Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Immunology, Processus de Transfert et d'Echanges dans l'Environnement - EA 3819 (PROTEE), Université de Toulon (UTLN), Heinrich-Pette-Institut, Leibniz Institute for Experimental Virology, Enrico Lugli and Pratip K. Chattopadhyay were supported by grants from the Fondazione Cariplo (Grant Ricerca Biomedica 2012/0683), the Italian Ministry of Health (Bando Giovani Ricercatori GR-2011-02347324) and the European Union Marie Curie Career Integration Grant 322093 (all to E.L.). E.L. and P.K.C. are International Society for the Advancement of Cytometry (ISAC) Marylou Ingram scholars. Alice Yue and Ryan R. Brinkman were funded by Genome BC and NSERC. Klaus Warnatz received funding from the German Federal Ministry of Education and Research (BMBF 01EO1303) and the Deutsche Forschungsgemeinschaft (DECIDE, DFG WA 1597/4-1 and the TRR130). The Jung laboratory is supported by funds of the ERC and ISF. Henrik Mei is a 2017-2021 ISAC scholar. Antonio Cosma is supported by the French government program: 'Investissement d'avenir: Equipements d'Excellence' (EQUIPEX)-2010 FlowCyTech, Grant number: ANR-10-EQPX-02-01. Henrik Mei is supported by the Deutsche Forschungsgemeinschaft (DFG, grants Me3644/5-1 and TRR130/TP24)., Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Università degli Studi di Firenze = University of Florence (UniFI)-DENOTHE Center, Institut Pasteur [Paris] (IP), Humboldt University Of Berlin, Universität Bonn = University of Bonn, Università degli studi di Genova = University of Genoa (UniGe), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Universität Leipzig, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Obstetrics & Gynecology, Rheumatology, Pediatrics, Landsteiner Laboratory, Other departments, AII - Inflammatory diseases, Università di Modena e Reggio Emilia, DENOTHE Center-University of Florence, Santa Lucia Foundation ( IRCCS ), International Occultation Timing Association European Section ( IOTA ES ), Fondazione Santa Lucia ( IRCCS ), BC Cancer Agency ( BCCRC ) -British Columbia Cancer Agency Research Centre, Fondazione don Carlo Gnocchi, Fondazione IRCCS, Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département d'Immunologie, Humboldt Universität zu Berlin, Universitat de Barcelona ( UB ), Charité, Weizmann Institute of Science, Université de Bonn, Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Singapore Immunology Network ( SIgN ), Agency for Science Technology and Research, College of Food Science and Technology, Centre for Transplantation, King's College London ( MRC ), Erasmus MC University Medical Center, Helmholtz Centre for Environmental Research ( UFZ ), Helmholtz Centre for Infection Research ( HZI ), University of Zürich [Zürich] ( UZH ) -Institute of Experimental Immunology [Zurich], Ludwig-Maximilians-Universität München, Johannes Gutenberg - Universität Mainz ( JGU ), Medical University of Vienna, Lymphopoïèse, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Johannes Gutenberg - University of Mainz ( JGU ), Processus de Transfert et d'Echanges dans l'Environnement - EA 3819 ( PROTEE ), Université de Toulon ( UTLN ), Universita degli studi di Genova, Cossarizza, Andrea, Chang, Hyun-Dong, Radbruch, Andrea, Akdis, Mübeccel, Andrä, Immanuel, Annunziato, Francesco, Bacher, Petra, Barnaba, Vincenzo, Battistini, Luca, Bauer, Wolfgang M., Baumgart, Sabine, Becher, Burkhard, Beisker, Wolfgang, Berek, Claudia, Blanco, Alfonso, Borsellino, Giovanna, Boulais, Philip E., Brinkman, Ryan R., Büscher, Martin, Busch, Dirk H., Bushnell, Timothy P., Cao, Xuetao, Cavani, Andrea, Chattopadhyay, Pratip K., Cheng, Qingyu, Chow, Sue, Clerici, Mario, Cooke, Anne, Cosma, Antonio, Cosmi, Lorenzo, Cumano, Ana, Dang, Van Duc, Davies, Derek, De Biasi, Sara, Del Zotto, Genny, Della Bella, Silvia, Dellabona, Paolo, Deniz, Günnur, Dessing, Mark, Diefenbach, Andrea, Di Santo, Jame, Dieli, Francesco, Dolf, Andrea, Donnenberg, Vera S., Dörner, Thoma, Ehrhardt, Götz R. A., Endl, Elmar, Engel, Pablo, Engelhardt, Britta, Esser, Charlotte, Everts, Bart, Dreher, Anita, Falk, Christine S., Fehniger, Todd A., Filby, Andrew, Fillatreau, Simon, Follo, Marie, Förster, Irmgard, Foster, John, Foulds, Gemma A., Frenette, Paul S., Galbraith, David, Garbi, Natalio, García-Godoy, Maria Dolore, Geginat, Jen, Ghoreschi, Kamran, Gibellini, Lara, Goettlinger, Christoph, Goodyear, Carl S., Gori, Andrea, Grogan, Jane, Gross, Mor, Grützkau, Andrea, Grummitt, Daryl, Hahn, Jona, Hammer, Quirin, Hauser, Anja E., Haviland, David L., Hedley, David, Herrera, Guadalupe, Herrmann, Martin, Hiepe, Falk, Holland, Tristan, Hombrink, Pleun, Houston, Jessica P., Hoyer, Bimba F., Huang, Bo, Hunter, Christopher A., Iannone, Anna, Jäck, Hans-Martin, Jávega, Beatriz, Jonjic, Stipan, Juelke, Kerstin, Jung, Steffen, Kaiser, Toralf, Kalina, Toma, Keller, Baerbel, Khan, Srijit, Kienhöfer, Deborah, Kroneis, Thoma, Kunkel, Désirée, Kurts, Christian, Kvistborg, Pia, Lannigan, Joanne, Lantz, Olivier, Larbi, Ani, LeibundGut-Landmann, Salome, Leipold, Michael D., Levings, Megan K., Litwin, Virginia, Liu, Yanling, Lohoff, Michael, Lombardi, Giovanna, Lopez, Lilly, Lovett-Racke, Amy, Lubberts, Erik, Ludewig, Burkhard, Lugli, Enrico, Maecker, Holden T., Martrus, Glòria, Matarese, Giuseppe, Maueröder, Christian, Mcgrath, Mairi, Mcinnes, Iain, Mei, Henrik E., Melchers, Fritz, Melzer, Susanne, Mielenz, Dirk, Mills, Kingston, Mirrer, David, Mjösberg, Jenny, Moore, Jonni, Moran, Barry, Moretta, Alessandro, Moretta, Lorenzo, Mosmann, Tim R., Müller, Susann, Müller, Werner, Münz, Christian, Multhoff, Gabriele, Munoz, Luis Enrique, Murphy, Kenneth M., Nakayama, Toshinori, Nasi, Milena, Neudörfl, Christine, Nolan, John, Nourshargh, Sussan, O'Connor, José-Enrique, Ouyang, Wenjun, Oxenius, Annette, Palankar, Raghav, Panse, Isabel, Peterson, Pärt, Peth, Christian, Petriz, Jordi, Philips, Daisy, Pickl, Winfried, Piconese, Silvia, Pinti, Marcello, Pockley, A. Graham, Podolska, Malgorzata Justyna, Pucillo, Carlo, Quataert, Sally A., Radstake, Timothy R. D. J., Rajwa, Bartek, Rebhahn, Jonathan A., Recktenwald, Diether, Remmerswaal, Ester B. M., Rezvani, Katy, Rico, Laura G., Robinson, J. Paul, Romagnani, Chiara, Rubartelli, Anna, Ruckert, Beate, Ruland, Jürgen, Sakaguchi, Shimon, Sala-de-Oyanguren, Francisco, Samstag, Yvonne, Sanderson, Sharon, Sawitzki, Birgit, Scheffold, Alexander, Schiemann, Matthia, Schildberg, Frank, Schimisky, Esther, Schmid, Stephan A., Schmitt, Steffen, Schober, Kilian, Schüler, Thoma, Schulz, Axel Ronald, Schumacher, Ton, Scotta, Cristiano, Shankey, T. Vincent, Shemer, Anat, Simon, Anna-Katharina, Spidlen, Josef, Stall, Alan M., Stark, Regina, Stehle, Christina, Stein, Merle, Steinmetz, Tobit, Stockinger, Hanne, Takahama, Yousuke, Tarnok, Attila, Tian, Zhigang, Toldi, Gergely, Tornack, Julia, Traggiai, Elisabetta, Trotter, Joe, Ulrich, Henning, van der Braber, Marlou, van Lier, René A. W., Veldhoen, Marcello, Vento-Asturias, Salvador, Vieira, Paulo, Voehringer, David, Volk, Hans-Dieter, von Volkmann, Konrad, Waisman, Ari, Walker, Rachael, Ward, Michael D., Warnatz, Klau, Warth, Sarah, Watson, James V., Watzl, Carsten, Wegener, Leonie, Wiedemann, Annika, Wienands, Jürgen, Willimsky, Gerald, Wing, Jame, Wurst, Peter, Yu, Liping, Yue, Alice, Zhang, Qianjun, Zhao, Yi, Ziegler, Susanne, Zimmermann, Jakob, Cossarizza, A., Chang, H., Radbruch, A., Akdis, M., Andrã¤, I., Annunziato, F., Bacher, P., Barnaba, V., Battistini, L., Bauer, W., Baumgart, S., Becher, B., Beisker, W., Berek, C., Blanco, A., Borsellino, G., Boulais, P., Brinkman, R., Bã¼scher, M., Busch, D., Bushnell, T., Cao, X., Cavani, A., Chattopadhyay, P., Cheng, Q., Chow, S., Clerici, M., Cooke, A., Cosma, A., Cosmi, L., Cumano, A., Dang, V., Davies, D., De Biasi, S., Del Zotto, G., Della Bella, S., Dellabona, P., Deniz, G., Dessing, M., Diefenbach, A., Di Santo, J., Dieli, F., Dolf, A., Donnenberg, V., Dã¶rner, T., Ehrhardt, G., Endl, E., Engel, P., Engelhardt, B., Esser, C., Everts, B., Dreher, A., Falk, C., Fehniger, T., Filby, A., Fillatreau, S., Follo, M., Fã¶rster, I., Foster, J., Foulds, G., Frenette, P., Galbraith, D., Garbi, N., García-Godoy, M., Geginat, J., Ghoreschi, K., Gibellini, L., Goettlinger, C., Goodyear, C., Gori, A., Grogan, J., Gross, M., Grã¼tzkau, A., Grummitt, D., Hahn, J., Hammer, Q., Hauser, A., Haviland, D., Hedley, D., Herrera, G., Herrmann, M., Hiepe, F., Holland, T., Hombrink, P., Houston, J., Hoyer, B., Huang, B., Hunter, C., Iannone, A., Jã¤ck, H., Jã¡vega, B., Jonjic, S., Juelke, K., Jung, S., Kaiser, T., Kalina, T., Keller, B., Khan, S., Kienhã¶fer, D., Kroneis, T., Kunkel, D., Kurts, C., Kvistborg, P., Lannigan, J., Lantz, O., Larbi, A., LeibundGut-Landmann, S., Leipold, M., Levings, M., Litwin, V., Liu, Y., Lohoff, M., Lombardi, G., Lopez, L., Lovett-Racke, A., Lubberts, E., Ludewig, B., Lugli, E., Maecker, H., Martrus, G., Matarese, G., Mauerã¶der, C., Mcgrath, M., Mcinnes, I., Mei, H., Melchers, F., Melzer, S., Mielenz, D., Mills, K., Mirrer, D., Mjã¶sberg, J., Moore, J., Moran, B., Moretta, A., Moretta, L., Mosmann, T., Mã¼ller, S., Mã¼ller, W., Mã¼nz, C., Multhoff, G., Munoz, L., Murphy, K., Nakayama, T., Nasi, M., Neudã¶rfl, C., Nolan, J., Nourshargh, S., O'Connor, J., Ouyang, W., Oxenius, A., Palankar, R., Panse, I., Peterson, P., Peth, C., Petriz, J., Philips, D., Pickl, W., Piconese, S., Pinti, M., Pockley, A., Podolska, M., Pucillo, C., Quataert, S., Radstake, T., Rajwa, B., Rebhahn, J., Recktenwald, D., Remmerswaal, E., Rezvani, K., Rico, L., Robinson, J., Romagnani, C., Rubartelli, A., Ruckert, B., Ruland, J., Sakaguchi, S., Sala-de-Oyanguren, F., Samstag, Y., Sanderson, S., Sawitzki, B., Scheffold, A., Schiemann, M., Schildberg, F., Schimisky, E., Schmid, S., Schmitt, S., Schober, K., Schã¼ler, T., Schulz, A., Schumacher, T., Scotta, C., Shankey, T., Shemer, A., Simon, A., Spidlen, J., Stall, A., Stark, R., Stehle, C., Stein, M., Steinmetz, T., Stockinger, H., Takahama, Y., Tarnok, A., Tian, Z., Toldi, G., Tornack, J., Traggiai, E., Trotter, J., Ulrich, H., van der Braber, M., van Lier, R., Veldhoen, M., Vento-Asturias, S., Vieira, P., Voehringer, D., Volk, H., von Volkmann, K., Waisman, A., Walker, R., Ward, M., Warnatz, K., Warth, S., Watson, J., Watzl, C., Wegener, L., Wiedemann, A., Wienands, J., Willimsky, G., Wing, J., Wurst, P., Liping, Y., Yue, A., Zhang, Q., Zhao, Y., Ziegler, S., and Zimmermann, J.

Subjects
0301 basic medicine, T-Lymphocytes, Cell Separation, T cell precursors, 0302 clinical medicine, Immunophenotyping, Human lymphopoiesis, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Non-U.S. Gov't, Immunologic Technique, medicine.diagnostic_test, Research Support, Non-U.S. Gov't, virus diseases, hemic and immune systems, False Positive Reaction, Cell sorting, Flow Cytometry, natural killer and innate lymphoid cells differentiation, 3. Good health, Research Design, [SDV.IMM]Life Sciences [q-bio]/Immunology, Human, Quality Control, medicine.drug_class, Immunology, Animals, Cell Proliferation, DNA, False Positive Reactions, Humans, RNA, Software, Guidelines as Topic, Immunologic Techniques, chemical and pharmacologic phenomena, Computational biology, Biology, Monoclonal antibody, Research Support, Article, Flow cytometry, N.I.H, 03 medical and health sciences, Immune system, Research Support, N.I.H., Extramural, medicine, early lymphoid progenitors, Journal Article, Mass cytometry, IMUNOLOGIA, Animal, Extramural, B cell ontogeny, 030104 developmental biology, T-Lymphocyte, Cytometry, 030215 immunology
Abstract

The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and sometimes esoteric instrument, the flow cytometer that is able to count hundreds of cells in a single second, and can provide repetitive results in a tireless manner. Given this, the possibility to analyse immune phenotypes in a variety of clinical conditions has changed the use of the flow cytometer, which was incidentally invented in the late 1960s to measure cellular DNA by using intercalating dyes, such as ethidium bromide. The epidemics of HIV/AIDS in the 1980s then gave a dramatic impulse to the technology of counting specific cells, since it became clear that the quantification of the number of peripheral blood CD4+ T cells was crucial to follow the course of the infection, and eventually for monitoring the therapy. As a consequence, the development of flow cytometers that had to be easy-to-use in all clinical laboratories helped to widely disseminate this technology. Nowadays, it is rare to find an immunological paper or read a conference abstract in which the authors did not use flow cytometry as the main tool to dissect the immune system and identify its fine and complex functions. Of note, recent developments have created the sophisticated technology of mass cytometry, which is able to simultaneously identify dozens of molecules at the single cell level and allows us to better understand the complexity and beauty of the immune system.

Published
2017

32. An optimized method to measure human FOXP3 + regulatory T cells from multiple tissue types using mass cytometry.

Author

Dawson NAJ, Lam AJ, Cook L, Hoeppli RE, Broady R, Pesenacker AM, and Levings MK

Subjects
Antigens immunology, Humans, Staining and Labeling methods, T-Lymphocytes, Regulatory immunology, CD4 Lymphocyte Count methods, Flow Cytometry methods, Forkhead Transcription Factors metabolism, T-Lymphocytes, Regulatory cytology
Abstract

We optimized a method to detect FOXP3 by mass cytometry and compared the resulting data to conventional flow cytometry. We also demonstrated the utility of the protocol to profile antigen-specific Tregs from whole blood, or Tregs from tissues such as cord blood, thymus and synovial fluid., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2018
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33. CD4+ Foxp3+ regulatory T cells suppress γδ T-cell effector functions in a model of T-cell-induced mucosal inflammation.

Author

Yurchenko E, Levings MK, and Piccirillo CA

Subjects
Animals, CD4 Antigens immunology, Colitis immunology, Immune Tolerance immunology, Interferon-gamma immunology, Interleukin-17 immunology, Interleukin-2 Receptor alpha Subunit immunology, Mice, Mice, Inbred C57BL, CD4-Positive T-Lymphocytes immunology, Forkhead Transcription Factors immunology, Immunity, Mucosal immunology, Inflammation immunology, Intestines immunology, Receptors, Antigen, T-Cell, gamma-delta immunology, T-Lymphocytes, Regulatory immunology
Abstract

CD4(+) CD25(+) Foxp3(+) regulatory T (T(REG) ) cells are critical mediators of peripheral immune tolerance, and abrogation of their function provokes a variety of autoimmune and inflammatory states including inflammatory bowel disease. In this study, we investigate the functional dynamics of T(REG) -cell responses in a CD4(+) T-cell-induced model of intestinal inflammation in αβ T-cell-deficient (TCR-β(-/-) ) hosts to gain insights into the mechanism and cellular targets of suppression in vivo. We show that CD4(+) T effector cell transfer into T-cell-deficient mice rapidly induces mucosal inflammation and colitis development, which is associated with prominent Th1 and Th17 responses. Interestingly, we unveil a prominent role for resident γδ T cells in mucosal inflammation as they promote Th1 and particularly Th17 responses in the early phase of inflammation, thus exacerbating colitis development. We further demonstrate that CD4(+) CD25(+) Foxp3(+) T(REG) cells readily inhibit these responses and mediate disease protection, which correlates with their accumulation in the draining LN and lamina propria. Moreover, T(REG) cells can directly suppress γδ T-cell expansion and cytokine production in vitro and in vivo, suggesting a pathogenic role of γδ T cells in intestinal inflammation. Thus, functional alterations in T(REG) cells provoke dysregulated CD4(+) and γδ T-cell responses to commensal antigens in the intestine., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2011
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34. Human CD4+ FOXP3+ regulatory T cells produce CXCL8 and recruit neutrophils.

Author

Himmel ME, Crome SQ, Ivison S, Piccirillo C, Steiner TS, and Levings MK

Subjects
Antibodies, Monoclonal immunology, Antibodies, Monoclonal pharmacology, Chemokines, CC metabolism, Chemokines, CXC metabolism, Chemotaxis drug effects, Culture Media, Conditioned pharmacology, Forkhead Transcription Factors genetics, Gene Expression Regulation immunology, Humans, Interleukin-2 Receptor alpha Subunit metabolism, Interleukin-8 genetics, Interleukin-8 immunology, Neutrophils cytology, Neutrophils drug effects, Transduction, Genetic, Chemotaxis immunology, Forkhead Transcription Factors metabolism, Interleukin-8 metabolism, Neutrophils immunology, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism
Abstract

One of the defining features of the majority of FOXP3(+) Tregs is their inability to produce typical T-cell-derived cytokines. Little is known, however, about their capacity to produce chemokines. As Tregs are constitutively present in, and rapidly traffic to, non-lymphoid tissues, we hypothesized that they may produce chemokines to direct the composition of cells that infiltrate inflamed tissues. Surprisingly, we found that Tregs produce high amounts of CXCL8 (IL-8), a potent neutrophil chemoattractant. Tregs also produced other CC and CXC family chemokines, including CCL2-5, CCL7, and CXCL10. Whereas ectopic expression of FOXP3 suppressed cytokine production, it significantly induced CXCL8. Moreover, supernatants from Tregs attracted neutrophils via a CXCL8-dependent mechanism. These data provide the first evidence that although classical Tregs are defined by their lack of proinflammatory cytokine production, they secrete significant quantities of chemokines and thus may have an unappreciated role in directing the recruitment of immune cells., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2011
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