93 results on '"Moretta A"'
Search Results
2. Human NK cells directly recognize Mycobacterium bovis via TLR2 and acquire the ability to kill monocyte-derived DC
- Author
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Marcenaro, Emanuela, Ferranti, Bruna, Falco, Michela, Moretta, Lorenzo, and Moretta, Alessandro
- Published
- 2008
3. Heterogeneity of TLR3 mRNA transcripts and responsiveness to poly (I:C) in human NK cells derived from different donors
- Author
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Sivori, Simona, Falco, Michela, Carlomagno, Simona, Romeo, Elisa, Moretta, Lorenzo, and Moretta, Alessandro
- Published
- 2007
4. NK-cell phenotype at interruption underlies widely divergent duration of CD4+-guided antiretroviral treatment interruption
- Author
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Bozzano, Federica, Nasi, Milena, Bertoncelli, Linda, Nemes, Elisa, Prati, Francesca, Marras, Francesco, Mussini, Cristina, Moretta, Lorenzo, Cossarizza, Andrea, and De Maria, Andrea
- Published
- 2011
- Full Text
- View/download PDF
5. GPR56 as a novel marker identifying the CD56dull CD16+ NK cell subset both in blood stream and in inflamed peripheral tissues
- Author
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Della Chiesa, Mariella, Falco, Michela, Parolini, Silvia, Bellora, Francesca, Petretto, Andrea, Romeo, Elisa, Balsamo, Mirna, Gambarotti, Marco, Scordamaglia, Francesca, Tabellini, Giovanna, Facchetti, Fabio, Vermi, William, Bottino, Cristina, Moretta, Alessandro, and Vitale, Massimo
- Published
- 2010
6. Functionally relevant decreases in activatory receptor expression on NK cells are associated with pulmonary tuberculosis in vivo and persist after successful treatment
- Author
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Bozzano, Federica, Costa, Paola, Passalacqua, Giovanni, Dodi, Ferdinando, Ravera, Silvia, Pagano, Gabriella, Canonica, Giorgio W., Moretta, Lorenzo, and De Maria, Andrea
- Published
- 2009
7. Natural killer cells kill human melanoma cells with characteristics of cancer stem cells
- Author
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Pietra, Gabriella, Manzini, Claudia, Vitale, Massimo, Balsamo, Mirna, Ognio, Emanuela, Boitano, Monica, Queirolo, Paola, Moretta, Lorenzo, and Mingari, Maria Cristina
- Published
- 2009
8. NK cells provide helper signal for CD8+ T cells by inducing the expression of membrane-bound IL-15 on DCs
- Author
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Morandi, Barbara, Mortara, Lorenzo, Carrega, Paolo, Cantoni, Claudia, Costa, Gregorio, Accolla, Roberto S., Mingari, Maria Cristina, Ferrini, Silvano, Moretta, Lorenzo, and Ferlazzo, Guido
- Published
- 2009
9. Peptides with dual binding specificity for HLA-A2 and HLA-E are encoded by alternatively spliced isoforms of the antioxidant enzyme peroxiredoxin 5
- Author
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Sensi, Marialuisa, Pietra, Gabriella, Molla, Alessandra, Nicolini, Gabriella, Vegetti, Claudia, Bersani, Ilaria, Millo, Enrico, Weiss, Elizabeth, Moretta, Lorenzo, Mingari, Maria Cristina, and Anichini, Andrea
- Published
- 2009
10. NKp44 expression, phylogenesis and function in non-human primate NK cells
- Author
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De Maria, Andrea, Ugolotti, Elisabetta, Rutjens, Erik, Mazza, Stefania, Radic, Luana, Faravelli, Alessandro, Koopman, Gerrit, Di Marco, Eddi, Costa, Paola, Ensoli, Barbara, Cafaro, Aurelio, Mingari, Maria Cristina, Moretta, Lorenzo, Heeney, Jonathan, and Biassoni, Roberto
- Published
- 2009
11. Potentiation of NK cell-mediated cytotoxicity in human lung adenocarcinoma: role of NKG2D-dependent pathway
- Author
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Le Maux Chansac, Béatrice, Missé, Dorothée, Richon, Catherine, Vergnon, Isabelle, Kubin, Marek, Soria, Jean-Charles, Moretta, Alessandro, Chouaib, Salem, and Mami-Chouaib, Fathia
- Published
- 2008
12. Methylprednisolone induces preferential and rapid differentiation of CD34+ cord blood precursors toward NK cells
- Author
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Vitale, Chiara, Cottalasso, Francesca, Montaldo, Elisa, Moretta, Lorenzo, and Mingari, Maria Cristina
- Published
- 2008
13. Isolation of a novel KIR2DL3-specific mAb: comparative analysis of the surface distribution and function of KIR2DL2, KIR2DL3 and KIR2DS2
- Author
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Vitale, Massimo, Carlomagno, Simona, Falco, Michela, Pende, Daniela, Romeo, Elisa, Rivera, Paola, Chiesa, Mariella Della, Mavilio, Domenico, and Moretta, Alessandro
- Published
- 2004
14. Dendritic cells: function (PP-024)
- Author
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G. Vukovic, X. Xu, A. Ludwig, Y. Ozaki, D. Wakita, J. Kwak, R. Fukui, M. Inaba, R. Cavaliere, E. Watari, Hiroki Takagi, P. Bird, Christine Hartoonian, Z. Ye, R. Conte, Aamir W. Khan, K. Maeda, D. Boveda Ruiz, N. A. Mabbott, Lorenzo Mortara, H. Weighardt, M. Chevallet, Y. Ophir, G. M. J. Bos, K. Kataoka, I. Carmi-Levy, Y. Ishii, J. Vanderlocht, S. Kamihira, J. Jeong, D. Khochenkov, S. Brix, W. T. V. Germeraad, Y. Ninomiya, M. Nakamura, H. Ehara, L. Bonifaz, B. Bozic, S. Sekine, R. Kobayashi, J. A. Hamerman, E. Rajnavölgyi, R. Luger, K. Masuko, S. Ikehara, G. Perez-Montesinos, Y. Wu, C. Yoon, J. Luu, Alessandro Moretta, M. A. Fernandez, B. Balint, G. J. Wathne, J. Farache, R. Spörri, E. V. Johnson, M. C. Canavan, R. S. Gilbert, S. Koizumi, W. Kratky, Meicheng Li, T. Takagi, C. Villers, A. Mantovani, Y. Miyachi, Y. Fukuyama, A. Rodriguez, D. Dissanayake, Maria Cristina Mingari, M. Fukui, T. Nishimura, M. Rimoldi, K. M. Murphy, C. H. M. J. Van Elssen, M. Mayumi, Y. Yu, J. M. Levitt, C. Takaku, A. Dragicevic, H. Amuro, N. Mohaghegh, T. Ikeda, S. Waseem, M. Matsuda, S. Koyasu, N. Hirata, I. Dunay, D. Vucevic, J. Sakabe, M. Naito, H. Shirasaki, K. Kim, H. Freitas, Y. Yagi, F. K. Puttur, H. Takahashi, Y. Bae, R. Mitamura, P. Y. Low, K. Inaba, T. Fekete, K. Miyake, E. Razin, N. Katoh, Y. Zhang, T. Yamashita, H. Gayum, T. Ito, E. Shinya, S. Yoon, O. Taguchi, H. Ito, A. Mendez-Reguera, K. Fujihashi, Y. Yanagawa, E. A. Lebedinskaya, T. Bito, M. S. J. Mangan, Y. Chen, D. Oliveri, N. Iriemenam, E. Traggiai, C. Catoni, M. Azuma, M. Mashayekhi, G. Shakhar, M. A. Miah, S. Vasilijic, K. Sugita, K. Shimamoto, Y. Tokura, Y. Ohshima, S. Weber, C. McCarthy, M. C. Nussenzweig, P. S. Ohashi, P. Huner, Yoonyoung Kim, M. Song, A. Fleig, M. Ogata, S. Huerta-Yepez, H. Yoshida, V. Savic, N. Kadowaki, J. Djokic, J. C. Dos Santos, P. W. H. Frings, E. A. Rivitti, A. Yoshimura, B. Meek, C. Fernandez, K. Onoé, Y. Bai, M. Ushida, S. Partida-Sanchez, P. Yang, C. Schuh, C. Loscher, Z. Zhan, K. Überla, I. Bonaccorsi, T. Iyoda, T. Kitawaki, A. Rizzitelli, H. Togashi, J. Rodrigo Mora, T. Takeshita, S. Valookaran, C. H. Huang, M. Jung, T. Lawrence, L. Xu, A. Szabo, J. Park, L. D. Sibley, H. Hall, M. Troye-Blomberg, M. H. Azor, M. R. Bono, S. Tomic, R. Yoshiki, I. Lange, Y. Katashiba, H. Kitamura, B. Rethi, W. Cheng, C. Kulen, S. Dahlström, X. Cao, M. Farinacci, M. Hirai, H. Sugimoto, J. Morser, T. Rabilloud, J. Lim, P. N. Marche, X. Liu, A. O. Kamphorst, N. K. Akhmatova, T. Uchiyama, C. M. Yang, E. Watanabe, L. Kaptue, G. Lui, N. Chalermsarp, W. Weninger, S. H. E. Kaufmann, A. Y. Ramirez Marmol, K. S. Akagawa, D. M. Kemeny, Mehdi Mahdavi, K. Sato, M. P. Seed, M. Ohtani, S. Jin, Roberto S. Accolla, H. Watarai, E. A. Futata, S. C. Hsu, R. Couderc, M. Matsumoto, R. Tamagawa-Mineoka, J. Matsumura, C. N. D'Alessandro-Gabazza, V. Martinez-Estrada, K. Okazaki, M. Colic, C. Chu, K. Kang, O. V. Lebedinskaya, H. Bhagat, A. Martini, L. Lu, K. H. Chow, S. Yona, R. Miyamoto, Y. Mori, A. Owaki, W. Tu, A. Vallon-Eberhard, B. Jux, A. Haydaroglu, P. L. Ho, Y. L. Lau, M. Satoh, R. Amakawa, P. Larghi, M. Tenbusch, A. Mount, N. Ryusuke, Z. Guo, R. Ignatius, E. Fu, N. Murakami, T. Seya, T. Fukaya, L. T. Wang, M. Hata, M. Toda, I. R. Ramachandran, C. Murphy, Lorenzo Moretta, M. M. Meredith, A. Kawakita, M. Satomi, C. Porta, A. Sica, H. Cortado, S. Fukuhara, B. Roediger, J De Calisto, H. H. Chen, P. A. Kalvanagh, C. Qian, A. Yasukawa, A. Sumoza-Toledo, S. Rho, S. Kadow, T. Felzmann, M. Yeom, D. Cavalieri, M. Mingari, M. Tsai, H. Diemer, M. Yasutomi, M. Rahman, D. You, M. Gershwin, A. Mancino, R. Penner, E. J. Villablanca, A. M. Dohnal, W. Song, K. Satoh, S. Matsuda, A. Takaori-Kondo, M. Rosemblatt, A. L. Cunningham, S. Hartmann, I. Majstorovic, S. Reece, T. Maeda, Paolo Carrega, P. Guiry, O. Aramaki, K. Y. Chua, S. Y. Chen, S. Kawabata, D. Dudziak, K. Kabashima, C. A. Jones, K. Iwabuchi, W. Zhang, I. Rajkovic, M. Shimizu, Y. Yao, J. N. Søndergaard, M. N. Sato, E. C. Gabazza, J. Jin, P. Uskokovic, E. Lee, R. Brandt, T. Dzopalic, Guido Ferlazzo, J. Wang, R. Huang, G. Chen, J. Cazarin-Barrientos, C. Arama, M. Eisenblätter, Massoumeh Ebtekar, B. Yang, M. Jang, C. OuYang, M. Gavrilova, F. Masson, J. Hopkins, R. White, H. Ogura, C. Esser, P. Milosavljevic, Y. Jiang, M. Taniguchi, H. Iwai, P. Guermonprez, H. Kagechika, Kayhan Azadmanesh, F. Jurado, A. Van Dorsselaer, M. Nussenzweig, Y. Miyake, T. Kim, A. J. S. Duarte, C. Maruta, G. Belz, M. V. Kiselevsky, M. Noguchi, L. Qian, D. Li, L. Beltrame, Barbara Morandi, F. D. Lourenço, B. Chiang, H. Yi, S. Xia, S. Hoshino, W. S. Blaner, S. Jung, S. Chmill, A. Yurtsever, E. Sidorova, M. Kanamori, and G. Qin
- Subjects
Chemistry ,Immunology ,Immunology and Allergy ,General Medicine ,Function (mathematics) ,Cell biology - Published
- 2010
15. NK cells and NK receptors (PP-007)
- Author
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L. Brossay, K. Hellstrand, M. Tashiro, Z. Tan, N. Yahaghi, N. Bercovici, F. Gong, S. Ferrone, M. Ostadali, S. Makino, M. H. Brown, S. Rahimifar, K. Shiozawa, Q. Sha, N. Yajima, H. Wang, A. Perier, K. Akashi, F. Shahsavar, S. Kamizono, Y. Hayakawa, L. Cui, A. Hashiramoto, G. Grosveld, G. Zheng, M. Kim, T. Hassan Ali, C. Fugere, F. Lee, B. R. Choi, A. Caignard, A. Serrano, S. del Toro-Arreola, O. Gonzalez-Ramella, H. Wei, F. Guimont-Desrochers, K. Mirjačić Martinović, N. Chiang, J. Haramati, C. H. Ribeiro, B. Escudier, T. Kishimoto, G. S. Duncan, H. M. Bond, M. Niam, S. Kim, P. S. Ohashi, P. Ramos-Gonzalez, J. Aurelius, T. W. Mak, D. Amre, Emily M. Mace, M. Fulciniti, H. Asanuma, C. Cohen, K. Izukuri, A. Piroozmand, T. Otsuki, S. Akira, L. C. Lit, Z. J. Cappello, A. Anichini, L. Jave-Suarez, Z. Hassan, S. H. Cheah, H. J. Woo, A. Rezaei, M. Molina, M. Montes-Casillas, B. Favier, Fumio Takei, T. Miyake, F. Ishikawa, G. Pittari, Evette A. Haddad, A. Vuletic, M. Mesuraca, O. Debbech, S. Zepeda-Morales, R. La Rocca, K. Saadati, X. Dong, S. Chu, N. Kumagai, E. F. Lind, H. Lin, M. Koh, K. Sato, N. Tajik, G. Suck, A. Morimoto, S. Ozawa, Y. Yang, E. Kubota, M. Chagnon, A. Ahmad, N. Matsumoto, T. Matsukura, Katherine A. Siminovitch, T. Kinoshita, H. Hayashi, D. R. Staines, B. Tsai, X. Zheng, K. Yoshida, M. Bustamante, N. Mousavinasab, Y. Nishimura, M. van Driel, A. Takashima, E. W. Brenu, A. Y. Kadin, T. Kakiuchi, T. Hu, S. Radenkovic, S. M. Marshall-Gradisnik, M. Chow, M. Maeda, T. Nakano, I. Andreeva, M. G. Seidel, G. Fregni, A. Sheikhi, K. Yamamoto, K. J. Ashton, Z. Tian, N. G. Clarkson, T. H. A. Almosawy, G. M. Konjevic, L. Catalano, C. Zhang, A. T. Look, L. Tadepally, C. Li, M. Galgani, C. Movitz, C. Lin, S. Ito, W. He, N. Erfani, Y. Kato, A. Mashida, J. Lee, F. Mehrabian, K. Suzuki, M. Irago, K. Matsushita, S. Han, H. Zhao, L. Cadavid, S. Huang, L. M. Kanevski, S. Farjadian, H. M. Cheng, M. F. Avril, A. Moretta, J. P. Haight, S. Samaran, K. Fukuoka, C. Ietto, Y. Tanaka, M. McDuffie, A. Bravo-Cuellar, M. Fuquen, F. Hosaini-nasab, B. Fu, F. Thorén, P. Li, P. C. Tan, S. Gad, C. Banh, S. Shiozawa, B. Rotoli, S. Lesage, H. Nikuinejad, M. Garcia-Chagollan, N. Collazo, N. Watanabe, E. Gulletta, R. Lotfi, C. Hernández, A. V. Klinkova, A. Iannello, G. Morrone, A. Aguilar-Lemarroy, L. Wu, C. Deslandres, Y. Hu, A. A. Akhiani, E. I. Kovalenko, B. Chiang, A. Ghaderi, J. Zhang, M. Cheng, J. Tang, E. Carbone, E. H. Kim, M. Bueno-Topete, R. Hata, Laura K. Senger, M. Garrido, O. Takeuchi, K. Hamada, K. Komai, C. Ma, R. Sun, D. Siemens, Z. Almalte, K. Alimoghaddam, T. Kuwabara, S. So, S. Ho, F. Zheng, and M. Fang
- Subjects
Chemistry ,Immunology ,Immunology and Allergy ,General Medicine ,Receptor ,Cell biology - Published
- 2010
16. Methylprednisolone induces preferential and rapid differentiation of CD34+ cord blood precursors toward NK cells
- Author
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Francesca Cottalasso, Elisa Montaldo, Chiara Vitale, Lorenzo Moretta, and Maria Cristina Mingari
- Subjects
Immunology ,CD34 ,Antigens, CD34 ,Biology ,Methylprednisolone ,Antigen-Antibody Reactions ,Interleukin 21 ,Humans ,Immunology and Allergy ,Cell Lineage ,Cells, Cultured ,Lymphokine-activated killer cell ,Janus kinase 3 ,Interleukin-8 ,Lymphocyte differentiation ,Antibodies, Monoclonal ,Cell Differentiation ,General Medicine ,Fetal Blood ,Hematopoietic Stem Cells ,NKG2D ,Cell biology ,Killer Cells, Natural ,Interleukin 12 ,Cytokines ,Female ,Neural cell adhesion molecule - Abstract
Previous studies showed that methylprednisolone (MePDN) down-regulates the surface expression of activating NK receptors and sharply inhibits the NK cytotoxicity both in vitro and in vivo. Since MePDN is administered to patients undergoing hemopoietic stem cell transplant to treat acute graft versus host disease (GvHD), we analyzed whether it could also inhibit the NK cell differentiation from CD34(+) hemopoietic cell precursors, thus interfering with the development of effector cells with anti-leukemic potential. We show that MePDN promotes the in vitro differentiation of CD161+CD56+/- immature NK cells by inducing a rapid expression of NKp46, NKG2D, DNAX-accessory molecule 1 (DNAM-1), leukocyte function-associated antigen-1 and NKG2A and an efficient cytolytic activity. This phenotypic and functional NK cell maturation occurred more rapidly than in parallel control cultures performed in the absence of MePDN. In addition, MePDN induced CD33+CD161-CD56- myeloid precursors to switch toward NK cells. It is also of note that immature NK cells when cultured in the absence (but not in the presence) of MePDN produced high amounts of IL-8. These data indicate that MePDN can accelerate the in vitro NK cell differentiation, thus revealing a dichotomous effect on immature versus mature NK cells; in addition, interference with the in vitro development of myeloid cells occurred. These effects should be further investigated in hemopoietic stem cell transplanted patients receiving steroids to treat GvHD.
- Published
- 2008
17. Isolation of a novel KIR2DL3-specific mAb: comparative analysis of the surface distribution and function of KIR2DL2, KIR2DL3 and KIR2DS2
- Author
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Paola Rivera, Michela Falco, Alessandro Moretta, Mariella Della Chiesa, Simona Carlomagno, Daniela Pende, Massimo Vitale, Elisa Romeo, and Domenico Mavilio
- Subjects
medicine.drug_class ,Immunology ,Cell ,Human leukocyte antigen ,Biology ,Transfection ,Monoclonal antibody ,Polymerase Chain Reaction ,Flow cytometry ,Receptors, KIR ,Antibody Specificity ,medicine ,Humans ,Immunology and Allergy ,Receptors, Immunologic ,Cells, Cultured ,medicine.diagnostic_test ,Histocompatibility Antigens Class I ,Antibodies, Monoclonal ,General Medicine ,Cytotoxicity Tests, Immunologic ,Flow Cytometry ,Molecular biology ,Killer Cells, Natural ,medicine.anatomical_structure ,Receptors, KIR2DL3 ,Polyclonal antibodies ,Receptors, KIR2DL2 ,biology.protein ,Immunoglobulin superfamily ,Function (biology) - Abstract
In recent years an increasing number of sequences coding for new KIRs have been described. However, the limited availability of mAbs with unique KIR specificities has hindered an exhaustive assessment of their actual function, HLA-specificity, expression at the cell surface and distribution in different cell populations. In this study we report the generation of a novel mAb (ECM41) specific for KIR2DL3 molecules. By the use of cell transfectants expressing one or other KIR we show that this reagent allows discrimination of KIR2DL3 from other GL183 mAb-reactive molecules such as KIR2DL2 and KIR2DS2. Moreover we show that this novel mAb can be used to assess the surface expression and distribution of KIR2DL3 in different polyclonal NK populations and in NK cell clones. Along this line, we were able to analyze the HLA class I specificity of NK clones expressing either KIR2DL3 or KIR2DL2, two inhibitory receptors that were so far serologically undistinguishable. Finally, the combined use of GL183 and ECM41 mAbs in redirected killing assays allowed us to investigate the functional outcome of the simultaneous engagement of KIR2DL3 and KIR2DS2 in NK cell clones co-expressing KIRs that display opposite (inhibitory vs activating) function.
- Published
- 2004
18. Regulatory role of NKp44, NKp46, DNAM-1 and NKG2D receptors in the interaction between NK cells and trophoblast cells. Evidence for divergent functional profiles of decidual versus peripheral NK cells
- Author
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Ezio Fulcheri, Lorenzo Moretta, Carola Prato, Alessandro Moretta, Maria Cristina Mingari, Paola Vacca, and Claudia Cantoni
- Subjects
Antigens, Differentiation, T-Lymphocyte ,Vascular Endothelial Growth Factor A ,Trophoblast cells ,Angiogenetic cytokines in pregnancy ,Decidual NK cells ,DNAM-1 ,Innate immunity in pregnancy ,NKG2D ,NKp44 ,NKp46 ,Immunology ,Cell Communication ,Biology ,Lymphocyte Activation ,Interleukin 21 ,Pregnancy ,medicine ,Decidua ,Immunology and Allergy ,Humans ,Natural Cytotoxicity Triggering Receptor 2 ,Natural Cytotoxicity Triggering Receptor 1 ,Janus kinase 3 ,Trophoblast ,General Medicine ,Cytotoxicity Tests, Immunologic ,Lymphocyte Subsets ,Cell biology ,Trophoblasts ,Killer Cells, Natural ,medicine.anatomical_structure ,Cell culture ,NK Cell Lectin-Like Receptor Subfamily K ,Interleukin 12 ,Cytokines ,Female ,K562 Cells ,K562 cells - Abstract
During the first trimester of pregnancy NK cells represent >50% of the lymphoid cells present in the human decidua where they reside in close contact with trophoblast cells. Because in decidual tissues NK cell activation and function may be induced by this interaction, we analyzed the cellular ligands recognized by activating NK receptors expressed on trophoblast cells. We show that these cells primarily express the NKp44 and DNAM-1 ligands and that interaction between these ligands and their corresponding receptors results in NK cell triggering. While activated peripheral blood NK (pNK) cells lysed the trophoblast cell lines JAR and JEG3, decidual NK (dNK) cells did not. On the other hand, they released VEGF, SDF-1, IP10 and large amounts of IL-8. Interaction with K562 target cells was exploited to induce optimal NK cell triggering, allowing a parallel, quantitative assessment of both cytolytic activity and cytokine production elicited by dNK cells. While dNK cells were unable to kill K562 even at high effector:target (E:T) ratios, they released large amounts of IL-8 also at low E:T ratios, a scenario compatible with dNK trophoblast cells interaction occurring within decidual tissues.
- Published
- 2008
19. Effect of superantigens on human thymocytes: selective proliferation of Vβ2+ cells in response to toxic shock syndrome toxin-1 and their deletion upon secondary stimulation
- Author
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Maria Cristina Mingari, Anna Cambiaggi, Vitale Chiara, Francesca Schiavetti, Rosa Bellomo, Alessandro Poggi, and L. Moretta
- Subjects
Staphylococcus aureus ,CD8 Antigens ,Receptors, Antigen, T-Cell, alpha-beta ,CD3 ,Bacterial Toxins ,Immunology ,Cell ,Clonal Deletion ,Thymus Gland ,Human leukocyte antigen ,Lymphocyte Activation ,Microbiology ,Enterotoxins ,Superantigen ,medicine ,Humans ,Immunology and Allergy ,Superantigens ,biology ,Chemistry ,Cell growth ,T-cell receptor ,Histocompatibility Antigens Class II ,Toxic shock syndrome toxin ,General Medicine ,Cytotoxicity Tests, Immunologic ,Molecular biology ,Clone Cells ,Thymocyte ,medicine.anatomical_structure ,Child, Preschool ,CD4 Antigens ,biology.protein ,T-Lymphocytes, Cytotoxic - Abstract
The effects of toxic shock syndrome toxin-1 (TSST-1) on human thymocytes and their CD4/CD8-defined subsets have been analyzed. Postnatal thymocyte cell suspensions were cultured with 5 ng/ml TSST-1 for different time intervals. A strong cell proliferation of CD3+/TCR+ cells, characterized by selective expansion of cells expressing TCR V beta 2, occurred. In these cultured thymocytes, V beta 2+ cells were detected in all subsets including CD4-CD8+ cells. CD4-CD8+ thymocyte populations (obtained by depletion of CD4+ cells) were further analyzed for their ability to directly respond to TSST-1. An efficient cell proliferation occurred; however, it was completely abrogated upon removal of HLA class II+ cells (representing 10% of fresh thymocytes depleted of CD4+ cells). The HLA class II dependency of TSST-1 mediated functions was further documented at the clonal level. Thus, in the presence of TSST-1, CD4-CD8+ V beta 2+ clones efficiently lysed the HLA class II+ Raji target cells but not the corresponding HLA class II- variant RJ 2.2.5. Analysis of the effect of TSST-1-induced secondary stimulation on cultured (V beta 2+-enriched) thymocytes resulted in a selective depletion of V beta 2+ cells due to apoptotic cell death.
- Published
- 1996
20. Physical and functional association of CD45 and CD3-TCR complex on CD1+ human thymocytes. Evidence that the engagement of CD45 molecules can prevent CD1+ thymocytes from apoptosis
- Author
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Alessandro Poggi, Nicoletta Pella, Claudia Cantoni, Maria Raffaella Zocchi, Lorenzo Moretta, and H. Wigzell
- Subjects
Programmed cell death ,CD8 Antigens ,CD3 ,Immunology ,Cell ,Population ,CD1 ,Apoptosis ,chemical and pharmacologic phenomena ,Thymus Gland ,Antigens, CD1 ,T-Lymphocyte Subsets ,medicine ,Humans ,Immunology and Allergy ,education ,Cells, Cultured ,education.field_of_study ,biology ,Chemistry ,Antibodies, Monoclonal ,hemic and immune systems ,General Medicine ,Molecular biology ,In vitro ,Cell biology ,Cross-Linking Reagents ,medicine.anatomical_structure ,Receptor-CD3 Complex, Antigen, T-Cell ,CD4 Antigens ,biology.protein ,Leukocyte Common Antigens ,CD8 ,Protein Binding - Abstract
In this study the effects of CD45 engagement on CD3-TCR-driven stimulation of CD1+ human immature thymocytes have been analyzed. Simultaneous cross-linking of CD45 and CD3 antigens on highly purified CD1+ thymocytes reduced the number of cells undergoing apoptosis after 16 h of in vitro culture. This cell population might represent immature thymocytes committed in vivo to die by programmed cell death (PCD). CD45 engagement could also increase the number of cycling CD1+ thymocytes; of note, the large majority (> 95%) of dividing cells expressed the CD1 molecule at the cell surface, indicating that proliferating cells were actually represented by immature thymocytes. These data suggest that the CD45 molecule might play a role in the rescue of immature thymocytes from PCD during differentiation. Along this line, we found that activation of CD1+ thymocytes via the CD3-TCR complex could be enhanced by CD45, both in terms of transcription and surface expression of IL-2R. These effects might be explained by the finding that the CD45 molecule (but not its isoforms CD45RO and RA) was physically associated with the CD3-TCR complex at the cell surface of CD1+ human thymocytes, as shown by co-precipitation and co-capping experiments. Finally, cross-linking of CD45 and CD3 antigens led to the expansion of CD3+ thymocytes co-expressing CD4 and CD8, indicating that simultaneous engagement of CD45 and CD3 molecules can block CD1+ cells at the double-positive (CD3+CD4+CD8+) differentiation stage. On the other hand, stimulation through CD3 resulted in the expansion of thymocytes showing a mature phenotype (CD3+CD4+ or CD3+CD8+). Altogether, these findings suggest that the CD45 molecule is involved both in early activation and in the regulation of CD1+ thymocyte differentiation.
- Published
- 1996
21. NK cells and NK receptors (WS-007)
- Author
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P. Carrega, A. Moretta, E. Vigorito, V. I. Schwierzeck, K. Furuyama-Tanaka, J. Chavarria, G. Pezzino, H. Prosser, B. D. Levy, P. Lane, M. Inlay, A. Bradley, D. Raulet, M. Falco, R. B. Jones, S. Sasawatari, N. Toyama-Sorimachi, Mario A. Ostrowski, D. Pende, Z. Zhou, D. Withers, J. Zhang, A. P. Makrigiannis, P. Lyons, Y. Mok, G. Ferlazzo, Douglas F. Nixon, M. Mingari, M. Cernadas, B. Hsiung, M. Yoshizaki, O. Haworth, T. Sasazuki, Jason D. Barbour, G. Desanti, J. Seita, C. Zhang, H. Karsunky, M. Wong, H. Jung, F. Colluci, Sandra López-Vergès, A. R. Jha, I. L. Weissman, J. W. Fathman, P. Queirolo, Z. Tian, K. Inaba, Brian Long, Lishomwa C. Ndhlovu, K. G. C. Smith, Lewis L. Lanier, L. Moretta, and D. Bhattacharya
- Subjects
Immunology ,Immunology and Allergy ,General Medicine - Published
- 2010
22. NK-cell phenotype at interruption underlies widely divergent duration of CD4+-guided antiretroviral treatment interruption
- Author
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Elisa Nemes, Cristina Mussini, Francesco Marras, Andrea Cossarizza, Milena Nasi, Lorenzo Moretta, Federica Bozzano, Andrea De Maria, Linda Bertoncelli, and Francesca Prati
- Subjects
Adult ,Male ,NK ,Immunology ,Cell ,HIV Infections ,Biology ,Drug Administration Schedule ,Cohort Studies ,HIV ,AIDS ,CD4 ,Immune system ,Acquired immunodeficiency syndrome (AIDS) ,medicine ,Antiretroviral treatment ,Immunology and Allergy ,Humans ,Longitudinal Studies ,Innate immune system ,Natural Cytotoxicity Triggering Receptor 1 ,General Medicine ,Drug holiday ,Middle Aged ,medicine.disease ,NKG2D ,Phenotype ,Immunity, Innate ,CD4 Lymphocyte Count ,Killer Cells, Natural ,medicine.anatomical_structure ,Anti-Retroviral Agents ,Gene Expression Regulation ,HIV-1 ,Female - Abstract
Long-term side effects may represent a relevant burden of antiretroviral treatment (ART) in HIV-infected patients with good CD4 immune reconstitution over extended time spans. CD4-guided treatment interruption (TI) has been evaluated to address this point and may result in a wide spectrum of time off ART in different patient cohorts. We studied whether differences in innate immune responses, in particular NK cells, are associated to patterns of longer (LoTI) or a shorter (ShTI) TI. Clinical cohort parameters were analyzed on a group of patients widely diverging for TI duration (9 versus18 months) on samples before TI, including NK-cell analysis and function by natural cytotoxicity receptor (NCR)-triggered γ-IFN production. Although persistently reduced NCR expression (NKp30) and function were observed in both LoTI and ShTI patients on ART compared with healthy donors, relevant differences were observed at baseline TI in those patients who subsequently developed LoTI course. Lower expression of NKG2D and NKp46 on NK cells. This also translates in reduced γ-IFN production in redirected functional assays. Thus, differences in innate immune balance exist during ART, may be associated to differential control of HIV infection and their understanding could explain clinical differences in individual patients that are not reflected by CD4(+) cell counts alone.
- Published
- 2011
23. Natural killer cells kill human melanoma cells with characteristics of cancer stem cells
- Author
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Lorenzo Moretta, Mirna Balsamo, Massimo Vitale, Paola Queirolo, Monica Boitano, Claudia Manzini, Emanuela Ognio, Maria Cristina Mingari, and Gabriella Pietra
- Subjects
Cytotoxicity, Immunologic ,Skin Neoplasms ,Immunology ,Nerve Tissue Proteins ,Receptors, Nerve Growth Factor ,Immunotherapy, Adoptive ,Interleukin 21 ,NK-92 ,Cancer stem cell ,Antigens, CD ,Cell Line, Tumor ,medicine ,Tumor Cells, Cultured ,Immunology and Allergy ,Humans ,AC133 Antigen ,neoplasms ,Melanoma ,Glycoproteins ,Lymphokine-activated killer cell ,biology ,CD117 ,Caspase 3 ,General Medicine ,medicine.disease ,Cell biology ,Killer Cells, Natural ,Proto-Oncogene Proteins c-kit ,biology.protein ,Interleukin 12 ,Neoplastic Stem Cells ,Interleukin-2 ,Stem cell ,Peptides - Abstract
Experimental and clinical data suggest that tumours harbour a cell population retaining stem cell characteristics that can drive tumorigenesis. CD133 is considered an important cancer stem cells (CSC)-associated marker. In a large variety of human malignancies, including melanoma, CD133(+) cells have been reported to comprise CSC. In this study, we show that melanoma cell lines are highly heterogeneous for the expression of several stem cell-associated markers including CD133, c-kit/CD117 and p75 neurotrophin receptor/CD271. Since no information is available on the ability of NK cells to recognize and lyse melanoma stem cells, we assessed whether melanoma cell lines, characterized by stem cell-like features, were susceptible to lysis by IL-2-activated NK cells. We show that activated NK cells efficiently kill malignant melanoma cell lines that were enriched in putative CSC by the use of different selection methods (i.e. CD133 expression, radioresistance or the ability to form melanospheres in stem cell-supportive medium). NK cell-mediated recognition and lysis of melanoma cells involved different combinations of activating NK receptors. Since CSC have been reported to be both drug resistant and radioresistant, our present data suggest that NK-based adoptive immunotherapy could represent a novel therapeutic approach to possibly eradicate metastatic melanoma.
- Published
- 2009
24. NK cells provide helper signal for CD8+ T cells by inducing the expression of membrane-bound IL-15 on DCs
- Author
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Guido Ferlazzo, Lorenzo Moretta, Gregorio Costa, Paolo Carrega, Maria Cristina Mingari, Lorenzo Mortara, Claudia Cantoni, Silvano Ferrini, Barbara Morandi, and Roberto S. Accolla
- Subjects
Interleukin-15 ,Lymphokine-activated killer cell ,Chemistry ,Receptors, Interleukin-15 ,T cell ,Janus kinase 3 ,Immunology ,General Medicine ,Dendritic Cells ,CD8-Positive T-Lymphocytes ,CD49b ,Cell biology ,Killer Cells, Natural ,Interleukin 21 ,Interferon-gamma ,medicine.anatomical_structure ,Cell Line, Tumor ,medicine ,Interleukin 12 ,Immunology and Allergy ,Cytotoxic T cell ,Humans ,Antigen-presenting cell ,Signal Transduction - Abstract
NK cell recognition of cells that do not express or express low amounts of MHC class I molecules results not only in direct killing of target cells but also in the generation of specific T cell responses consequent to the induction of dendritic cell (DC) activation. While IL-12 production by NK cell-activated DCs is generally thought to play a critical role, a similar DC-mediated NK cell help has been reported also in IL-12-knockout mice. Here, we show that human NK cells can induce on DC surface membrane, via IFN-gamma secretion, the expression of high levels of IL-15. Remarkably, we show that DC expression of this membrane-bound form of IL-15, which is only partially associated with IL-15R molecules, is essential to promote specific CD8(+) T lymphocyte response in the absence of DC-derived IL-12.
- Published
- 2009
25. Peptides with dual binding specificity for HLA-A2 and HLA-E are encoded by alternatively spliced isoforms of the antioxidant enzyme peroxiredoxin 5
- Author
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Claudia Vegetti, Alessandra Molla, Marialuisa Sensi, Enrico Millo, Andrea Anichini, Maria Cristina Mingari, Gabriella Pietra, Ilaria Bersani, Lorenzo Moretta, Elizabeth H. Weiss, and Gabriella Nicolini
- Subjects
Gene isoform ,Immunology ,Amino Acid Motifs ,Human leukocyte antigen ,Biology ,Epitope ,Antioxidants ,HLA-E ,Antigens, Neoplasm ,HLA Antigens ,Catalytic Domain ,Cell Line, Tumor ,HLA-A2 Antigen ,Immunology and Allergy ,Humans ,Protein Isoforms ,Cysteine ,Melanoma ,Sequence Deletion ,Immunity, Cellular ,cDNA library ,Protein Stability ,Alternative splicing ,Histocompatibility Antigens Class I ,General Medicine ,Peroxiredoxins ,Molecular biology ,Clone Cells ,Killer Cells, Natural ,CTL ,Alternative Splicing ,Oxidative Stress ,Peroxiredoxin ,Peptides ,Protein Binding ,T-Lymphocytes, Cytotoxic - Abstract
Peptides with dual binding specificity for classical HLA class I and non-classical HLA-E molecules have been identified in virus-encoded proteins, but not in cellular proteins from normal or neoplastic cells. Expression screening of a melanoma cDNA library with a CTL clone recognizing an HLA-A2-restricted tumor-specific epitope encoded by mutant peroxiredoxin 5 (Prdx5), a stress-inducible peroxidase, led to the identification of two alternatively spliced isoforms of the same gene. These isoforms, which lack the catalytic cysteine fundamental for enzymatic activity, showed widespread expression in neoplastic and normal tissues but were unstable at the protein level, being detectable, following transient transfection, only after lactacystin treatment to inhibit proteasomal degradation. Isoform-specific sequences which formed, respectively, as result of exon 1 splicing to either exon 3 or 4, encoded two distinct nonapeptides (AMAPIKTHL and AMAPIKVRL, not present in the full-length protein) with anchor residues for HLA-A2 and HLA-E molecules and able to stabilize HLA-A2 and HLA-E cell surface expression. HLA-E+ targets, loaded with these peptides, were not recognized by NK cells expressing CD94/NKG2A inhibitory or CD94/NKG2C activatory receptors. However, both peptides were recognized, although with low avidity, by HLA-E-restricted CD8+ CTL. The nonapeptide AMAPIKVRL was used to elicit HLA-A2-restricted CTL clones that killed peptide-pulsed lymphoblastoid cell lines and melanoma cells expressing the corresponding Prdx5 isoform. Our results suggest that alternatively spliced isoforms of Prdx5, through the generation of HLA-E- and HLA-A2-restricted peptides may be part of immune-mediated stress response contributing to the detection and elimination of damaged normal or neoplastic cells.
- Published
- 2009
26. Expression of CD45 isoforms by fresh and activated human γδ T lymphocytes and natural killer cells
- Author
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Eric Braakman, Els Sturm, Kitty Vijverberg, Brigitte A. van Krimpen, Jan. W. Gratama, Reinder L. H. Bolhuis, and L. Moretta
- Subjects
Lymphocyte ,Immunology ,chemical and pharmacologic phenomena ,In Vitro Techniques ,Lymphocyte Activation ,complex mixtures ,Antigens, CD ,T-Lymphocyte Subsets ,immune system diseases ,Aldesleukin ,Histocompatibility Antigens ,hemic and lymphatic diseases ,medicine ,Humans ,Immunology and Allergy ,Delta cell ,Lymphokine-activated killer cell ,Chemistry ,ZAP70 ,Receptors, Antigen, T-Cell, gamma-delta ,hemic and immune systems ,General Medicine ,T lymphocyte ,Natural killer T cell ,Molecular biology ,Killer Cells, Natural ,Delta II ,Phenotype ,medicine.anatomical_structure ,Leukocyte Common Antigens - Abstract
Naive and primed alpha beta T cells can be distinguished on the basis of their differential expression of CD45RA and CD45RO, respectively. The present study indicates that these CD45-isoforms also identify naive and primed maturational stages of gamma delta T cells and natural killer (NK) cells. In peripheral blood, all V gamma 9-V delta 2 gamma delta T cells reportedly express CD45RO whereas all V delta gamma delta T cells lack CD45RO. Here, we show that these CD45RO- V delta gamma delta T cells all express CD45RA and the CD45RO+ V.9-V delta 2 gamma delta cells lack expression of CD45RA. The V delta T cells acquired CD45RO expression and lost part of their surface CD45RA, following in vitro activation with phytohaemagglutinin or IL-2. Also the CD3-CD16+ NK cells in peripheral blood that are uniformly CD45RA+ CD45RO- completely converted to the CD45RA-CD45RO+ phenotype upon in vitro activation. Moreover, all cloned V.9-V delta 2 and V delta 1 T cells and NK cells express CD45RO and lack expression of CD45RA. Our results strongly suggest that CD45RA and CD45RO are genuine markers for naive and primed lymphocytes that represent distinct differentiation lineages.
- Published
- 1991
27. An analysis of α/β TCR V gene expression in the human thymus
- Author
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Johan Grunewald, R. Nirmal Shankar, Hans Wigzell, Carl Harald Janson, and L. Moretta
- Subjects
MHC class II ,biology ,Chemistry ,Immunology ,T-cell receptor ,Alpha (ethology) ,General Medicine ,Molecular biology ,Umbilical cord ,medicine.anatomical_structure ,Gene expression ,medicine ,biology.protein ,Immunology and Allergy ,Beta (finance) ,Gene ,CD8 - Abstract
We have previously analysed alpha/beta T cell receptor (TCR) V gene usage in CD4+ and CD8+ subpopulations from human peripheral blood lymphocytes (PBL) and umbilical cord blood, and described a biased usage of some of the TCR V beta genes towards the CD4+ subpopulation. In this report, the TCR V gene usage in single positive (SP) CD4+ or CD8+ human thymocytes was analysed. Three previously described mAb with a biased usage in PBL and umbilical cord blood also had a skewed reactivity towards the CD4+ subpopulation in SP human thymocytes. Thus, in all 12 cases V beta 5.1 and V beta 6.7, and in 11/12 cases V beta 12 were preferentially used in the CD4+CD8-, compared to the CD4-CD8+ thymic subpopulation. Altogether, these results suggest a selection process in the thymus, supposedly through the positive influence of MHC class II determinants, to be responsible for this non-random, skewed TCR V gene usage.
- Published
- 1991
28. General role of HLA class I molecules in the protection of target cells from lysis by natural killer cells: evidence that the free heavy chains of class I molecules are not sufficient to mediate the protective effect
- Author
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Massimo Vitale, Daniela Pende, Alessandro Moretta, C Di Donato, L. Nanni, Ermanno Ciccone, Simona Sivori, Lorenzo Moretta, O. Viale, and A. Beretta
- Subjects
Cytotoxicity, Immunologic ,medicine.drug_class ,Macromolecular Substances ,Immunology ,Mast-Cell Sarcoma ,Human leukocyte antigen ,HLA-C Antigens ,Monoclonal antibody ,Transfection ,Immunoglobulin Fab Fragments ,Mice ,L Cells ,Antigen ,medicine ,Tumor Cells, Cultured ,Immunology and Allergy ,Animals ,Humans ,B cell ,Alleles ,Cell Line, Transformed ,HLA-A Antigens ,Chemistry ,Histocompatibility Antigens Class I ,Antibodies, Monoclonal ,General Medicine ,Natural killer T cell ,Molecular biology ,Isotype ,Recombinant Proteins ,Killer Cells, Natural ,Cytolysis ,medicine.anatomical_structure ,Self Tolerance ,Immunoglobulin M ,HLA-B Antigens ,Immunoglobulin G ,beta 2-Microglobulin ,Alpha chain - Abstract
Some HLA-C alleles have been shown to exert a specific protective effect preventing target cells from lysis by groups of natural killer (NK) clones displaying a defined specificity. In this study, we analyzed whether class I-mediated protection is a more general phenomenon involving all NK cells. First, we utilized two anti-class I mAbs (6A4 of IgG1 isotype and A6-136 of IgM isotype), which had been shown to induce lysis of protected target cells by group 1 and group 2 NK clones. Addition of A6-136 or 6A4 used as F(ab')2 mAb resulted in lysis of protected target cells by all NK clones analyzed. Target cells were represented by a panel of HLA homozygous Epstein-Barr virus-transformed B cell lines (B-EBV) while NK clones were representative of clones displaying different GL183/EB6 surface phenotypes and/or different abilities to lyse allogeneic cells. Unselected NK clones derived from seven different individuals were tested against autologous target cells represented by phytohemagglutinin-induced blasts or B-EBV transformed cell lines. In both instances, addition of a mixture of 6A4 F(ab')2 and A6-136 mAbs resulted in lysis of autologous target cells, thus suggesting that class I molecules prevent lysis of normal cells by self NK cells. We further investigated whether the class I-mediated protection requires the complexed form of class I molecules (composed of alpha chain, beta 2-microglobulin and the antigen peptide) or rather the free alpha chain. Acidic treatment of the C1R (Cw4+) target cells or 81.22 (Cw3+, Cw4+) at pH 2.2 resulted in loss of reactivity with 6A4, A6-136 and W6-32 mAb (known to react with the assembled form of class I molecules) and in the de novo reactivity with L31 mAb (specific for the HLA-C free chain). While the untreated Cw+ C1R cells were resistant to lysis by the Cw4-specific group 1 NK clones, the pH 2.2-treated cells became highly susceptible to lysis by the same clones. These data indicate that, at least for the NK clones analyzed, the protection of target cells requires class I molecules in the complexed form.
- Published
- 1995
29. Bone marrow transplantation and graft versus host disease (WS-077)
- Author
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T. Oshima, E. Kakenaka, Y. Chen, A. Matsubara, H. Saji, K. Harada, M. Derogar, H. Abdelrazik, Makoto Kurachi, G. Awong, M. Koyama, T. Yabe, M. Satake, K. Nakajima, Y. Morishima, M. Onizuka, K. Tomizuka, K. Shibuya, K. Akashi, G. Spaggiari, A. Ogawa, K. Shibata, A. Shibuya, D. L. French, L. Moretta, Satoshi Ueha, O. Ringdén, G. Ma, G. Keller, Y. Wang, Z. Zhou, P. Pan, T. Nakamoto, H. Kai, P. Ljungman, S. Takashima, C. M. Divino, T. Nabekura, S. Ogawa, S. Eisenstein, Kouji Matsushima, Y. Yamashita, J. Abe, J. Zuniga-Pflucker, M. Takanashi, S. Chen, T. Sasazuki, S. Honda, K. Hirayasu, K. Kashiwase, S. Tahara-Hanaoka, Takanori Teshima, Y. Kodera, B. Omazic, Yusuke Shono, M. Kadowaki, and K. Aoyama
- Subjects
medicine.medical_specialty ,Graft-versus-host disease ,Bone marrow transplantation ,business.industry ,Immunology ,medicine ,Immunology and Allergy ,General Medicine ,medicine.disease ,business ,Surgery - Published
- 2010
30. Cell therapy (SY5-1)
- Author
-
Jacques Banchereau, P. Greenberg, T. Nakayama, S. Motohashi, G. Ragnarrson, L. Moretta, S. Strober, A. Palucka, S. Fujii, J. Blattman, Yves Levy, A. Uccelli, C. Fowler, Sangkon Oh, Hideki Ueno, Gerard Zurawski, Joseph W. Fay, A. Schietinger, L. Sloan, Masaru Taniguchi, T. Schmitt, I. Stromnes, and C. Chou
- Subjects
Cell therapy ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Immunology ,medicine ,Immunology and Allergy ,General Medicine ,business - Published
- 2010
31. Conserved TCR usage by HLA-Cw* 1601-restricted T cell clones recognizing melanoma antigens
- Author
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Cinthia Farina, Pierre van der Bruggen, Pascale Boël, Giorgio Parmiani, Marialuisa Sensi, and L Moretta
- Subjects
DNA, Complementary ,T cell ,Receptors, Antigen, T-Cell, alpha-beta ,Immunology ,Molecular Sequence Data ,chemical and pharmacologic phenomena ,Human leukocyte antigen ,Biology ,Epitope ,Epitopes ,Antigen ,Antigens, Neoplasm ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Humans ,Amino Acid Sequence ,Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ,Melanoma ,T-cell receptor ,hemic and immune systems ,General Medicine ,Virology ,Clone Cells ,Neoplasm Proteins ,CTL ,medicine.anatomical_structure ,Melanoma-Specific Antigens ,Alpha chain ,Follow-Up Studies ,T-Lymphocytes, Cytotoxic - Abstract
In this study we determined TCR alpha and beta chain nucleotide sequences of HLA-Cw*1601-restricted cytotoxic T lymphocyte (CTL) clones obtained from the peripheral blood lymphocytes (PBL) of a melanoma patient. These clones were previously shown to be involved in the recognition of melanoma-associated antigenic epitopes SAYGEPRKL and AARAVFLAL encoded by gene MAGE-1 and BAGE respectively. All (3/3) anti-MAGE-1 CTL clones displayed TCRBV5 usage and one clonotype was found twice, >1 year apart, in patient's PBL. Two out of three anti-BAGE CTL clones showed the same TCRAV/AJ and TCRBV/BJ combinations and differed in the alpha chain CDR3 for two residues and in the beta chain CDR3 for a single nucleotide which, however, did not change translation, These results suggest a pattern of TCR conservation in CTL selected for recognition of MAGE-1 or BAGE peptides on the autologous melanoma.
- Published
- 1996
32. GPR56 as a novel marker identifying the CD56dull CD16+ NK cell subset both in blood stream and in inflamed peripheral tissues
- Author
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Della Chiesa, Mariella, primary, Falco, Michela, additional, Parolini, Silvia, additional, Bellora, Francesca, additional, Petretto, Andrea, additional, Romeo, Elisa, additional, Balsamo, Mirna, additional, Gambarotti, Marco, additional, Scordamaglia, Francesca, additional, Tabellini, Giovanna, additional, Facchetti, Fabio, additional, Vermi, William, additional, Bottino, Cristina, additional, Moretta, Alessandro, additional, and Vitale, Massimo, additional
- Published
- 2009
- Full Text
- View/download PDF
33. General role of HLA class I molecules in the protection of target cells from lysis by natural killer cells: evidence that the free heavy chains of class I molecules are not sufficient to mediate the protective effect
- Author
-
Ciccone, Ermanno, primary, Pende, Daniela, additional, Nannl, Luca, additional, Donato, Carolina Di, additional, Viale, Oriane, additional, Beretta, Alberto, additional, Vitale, Massimo, additional, Sivori, Simona, additional, Moretta, Alessandro, additional, and Moretta, Lorenzo, additional
- Published
- 1995
- Full Text
- View/download PDF
34. Corrigendum
- Author
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Francesca Cottalasso, Elisa Montaldo, Maria Cristina Mingari, Lorenzo Moretta, and Chiara Vitale
- Subjects
Pathology ,medicine.medical_specialty ,Methylprednisolone ,Cord blood ,Immunology ,CD34 ,medicine ,Immunology and Allergy ,General Medicine ,Biology ,medicine.drug - Published
- 2008
35. The leukocyte Ig-like receptor (LIR)-1 for the cytomegalovirus UL18 protein displays a broad specificity for different HLA class I alleles: analysis of LIR-1+ NK cell clones.
- Author
-
Vitale, M, Castriconi, R, Parolini, S, Pende, D, Hsu, M-L, Moretta, L, Cosman, D, and Moretta, A
- Abstract
Leukocyte Ig-like receptor (LIR)-1 is a member of the Ig superfamily which has been shown to bind the human cytomegalovirus MHC class I homologue UL-18 protein. In this study, we have analyzed the expression and function of LIR-1 in human NK cells. We show that LIR-1 is expressed by a subset of NK cells variable in size among different donors. When compared to the known HLA class I-specific NK receptors, the expression of LIR-1 was found to be partially overlapped with that of CD94-NKG2A or with that of killer inhibitory receptors (KIR) belonging to the Ig superfamily. The use of the soluble form of UL-18 molecule revealed, in double fluorescence analysis, a selective binding to LIR-1+ cells while no correlation was observed between expression of either KIR or CD94-NKG2A molecules and ability to bind UL18. We further determined whether LIR-1 could also function as receptor for HLA class I molecules. To this end, we assessed the capability of LIR-1+ NK cell clones of lysing HLA class I- target cells transfected with different class I alleles, including HLA-A, -B, -C and -G alleles. Data revealed that LIR-1 functions as a broad HLA class I-specific inhibitory receptor recognizing different alleles coded for by different HLA loci. [ABSTRACT FROM PUBLISHER]
- Published
- 1999
- Full Text
- View/download PDF
36. Conserved TCR usage by HLA-Cw*1601-restricted T cell clones recognizing melanoma antigens
- Author
-
Farina, Cinthia, primary, van der Bruggen, Pierre, additional, Boël, Pascale, additional, Parmiani, Giorgio, additional, Sensi, Marialuisa, additional, and Moretta, L, additional
- Published
- 1996
- Full Text
- View/download PDF
37. Physical and functional association of CD45 and CD3-TCR complex on CD1+ human thymocytes. Evidence that the engagement of CD45 molecules can prevent CD1+ thymocytes from apoptosis
- Author
-
Poggi, Alessandro, primary, Pella, Nicoletta, additional, Cantoni, Claudia, additional, Zocchi, Maria Raffaella, additional, Moretta, Lorenzo, additional, and Wigzell, H., additional
- Published
- 1996
- Full Text
- View/download PDF
38. Effect of superantigens on human thymocytes: selective proliferation of Vβ2+ cells in response to toxic shock syndrome toxin-1 and their deletion upon secondary stimulation
- Author
-
Mingari, Maria Cristina, primary, Cambiaggi, Anna, additional, Chiara, Vitale, additional, Schiavetti, Francesca, additional, Bellomo, Rosa, additional, Poggi, Alessandro, additional, and Moretta, L., additional
- Published
- 1996
- Full Text
- View/download PDF
39. The leukocyte Ig-like receptor (LIR)-1 for the cytomegalovirus UL18 protein displays a broad specificity for different HLA class I alleles: analysis of LIR-1 + NK cell clones.
- Author
-
Vitale, M, Castriconi, R, Parolini, S, Pende, D, Hsu, M L, Moretta, L, Cosman, D, and Moretta, A
- Abstract
Leukocyte Ig-like receptor (LIR)-1 is a member of the Ig superfamily which has been shown to bind the human cytomegalovirus MHC class I homologue UL-18 protein. In this study, we have analyzed the expression and function of LIR-1 in human NK cells. We show that LIR-1 is expressed by a subset of NK cells variable in size among different donors. When compared to the known HLA class I-specific NK receptors, the expression of LIR-1 was found to be partially overlapped with that of CD94-NKG2A or with that of killer inhibitory receptors (KIR) belonging to the Ig superfamily. The use of the soluble form of UL-18 molecule revealed, in double fluorescence analysis, a selective binding to LIR-1 + cells while no correlation was observed between expression of either KIR or CD94-NKG2A molecules and ability to bind UL18. We further determined whether LIR-1 could also function as receptor for HLA class I molecules. To this end, we assessed the capability of LIR-1 + NK cell clones of lysing HLA class I- target cells transfected with different class I alleles, including HLA-A, -B, -C and -G alleles. Data revealed that LIR-1 functions as a broad HLA class I-specific inhibitory receptor recognizing different alleles coded for by different HLA loci.
- Published
- 1999
- Full Text
- View/download PDF
40. An analysis of α/β TCR V gene expression in the human thymus
- Author
-
Grunewald, Johan, primary, Shankar, R. Nirmal, additional, Wigzell, Hans, additional, Janson, Carl Harald, additional, and Moretta, L., additional
- Published
- 1991
- Full Text
- View/download PDF
41. Expression of CD45 isoforms by fresh and activated human γδ T lymphocytes and natural killer cells
- Author
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Braakman, Eric, primary, Sturm, Els, additional, Vijverberg, Kitty, additional, van Krimpen, Brigitte A., additional, Gratama, Jan. W., additional, Bolhuis, Reinder L. H., additional, and Moretta, L., additional
- Published
- 1991
- Full Text
- View/download PDF
42. Potentiation of NK cell-mediated cytotoxicity in human lung adenocarcinoma: role of NKG2D-dependent pathway.
- Author
-
Chansac, Béatrice Le Maux, Missé, Dorothée, Richon, Catherine, Vergnon, Isabelle, Kubin, Marek, Soria, Jean-Charles, Moretta, Alessandro, Chouaib, Salem, and Mami-Chouaib, Fathia
- Subjects
CELLS ,CANCER cells ,CELL lines ,ADENOCARCINOMA ,CELL-mediated cytotoxicity ,CARRIER proteins - Abstract
Natural cytotoxicity receptors and NKG2D correspond to major activating receptors involved in triggering of tumor cell lysis by human NK cells. In this report, we investigated the expression of NKG2D ligands (NKG2DLs), MHC class I-related chain (MIC) A, MICB and UL16-binding proteins 1, 2 and 3, on a panel of human non-small-cell lung carcinoma cell lines, and we analyzed their role in tumor cell susceptibility to NK cell lysis. Although adenocarcinoma (ADC) cells expressed heterogeneous levels of NKG2DLs, they were often resistant to NK cell-mediated killing. Resistance of a selected cell line, ADC-Coco, to allogeneic polyclonal NK cells and autologous NK cell clones correlated with shedding of NKG2DLs resulting from a matrix metalloproteinase (MMP) production. Treatment of ADC-Coco cells with a MMP inhibitor (MMPI) combined with IL-15 stimulation of autologous NK cell clones lead to a potentiation of NK cell-mediated cytotoxicity. This lysis is mainly NKG2D mediated, since it is abrogated by anti-NKG2D-neutralizing mAb. These results suggest that MMPIs, in combination with IL-15, may be useful for overcoming tumor cell escape from the innate immune response. [ABSTRACT FROM PUBLISHER]
- Published
- 2008
- Full Text
- View/download PDF
43. Isolation of a novel KIR2DL3-specific mAb: comparative analysis of the surface distribution and function of KIR2DL2, KIR2DL3 and KIR2DS2.
- Author
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Massimo Vitale, Simona Carlomagno, Michela Falco, Daniela Pende, Elisa Romeo, Paola Rivera, Mariella Della Chiesa, Domenico Mavilio, and Alessandro Moretta
- Abstract
In recent years an increasing number of sequences coding for new KIRs have been described. However, the limited availability of mAbs with unique KIR specificities has hindered an exhaustive assessment of their actual function, HLA-specificity, expression at the cell surface and distribution in different cell populations. In this study we report the generation of a novel mAb (ECM41) specific for KIR2DL3 molecules. By the use of cell transfectants expressing one or other KIR we show that this reagent allows discrimination of KIR2DL3 from other GL183 mAb-reactive molecules such as KIR2DL2 and KIR2DS2. Moreover we show that this novel mAb can be used to assess the surface expression and distribution of KIR2DL3 in different polyclonal NK populations and in NK cell clones. Along this line, we were able to analyze the HLA class I specificity of NK clones expressing either KIR2DL3 or KIR2DL2, two inhibitory receptors that were so far serologically undistinguishable. Finally, the combined use of GL183 and ECM41 mAbs in redirected killing assays allowed us to investigate the functional outcome of the simultaneous engagement of KIR2DL3 and KIR2DS2 in NK cell clones co-expressing KIRs that display opposite (inhibitory vs activating) function. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
44. p40 molecule regulates NK cell activation mediated by NK receptors for HLA class I antigens and TCR-mediated triggering of T lymphocytes.
- Author
-
Poggi, Alessandro, Tomasello, Elena, Revello, Valentino, Nanni, Luca, Costa, Paola, and Moretta, Lorenzo
- Abstract
p40 was previously described as a regulatory molecule capable of inhibiting both the natural and the CD16-mediated cytotoxicity of NK cells. In this study, we analyze the effect of p40 molecule engagement on the NK cell triggering induced by activating HLA class I-specific NK receptors (NKR) or on TCRαβ-mediated T cell activation. CD3
– CD16+ NK cell clones expressing activating NKR (either CD94 or p50) were analyzed in a redirected killing assay using P815 target cells and appropriate mAb. A strong target cell lysis was detected in the presence of anti-NKR or anti-CD16 mAb alone. Addition of anti-p40 mAb resulted in a strong inhibition of both anti-NKR or anti-CD16 mAb-induced cytolysis. mAb specific for either CD45 or lymphocyte function associated antigen-1 did not exert any inhibitory effect in the same experimental system. Free intracellular calcium ([Ca2 +]i) increase induced by mAb cross-linking of activating CD94 or p50 was inhibited by simultaneous engagement of p40 molecules, but not of other NK surface molecules including CD44 and CD56. In addition, cross-linking of p40 molecules strongly inhibited the CD94-induced tumor necrosis factor-α and IFN-γ production. Analysis of TCR αβ or γδ T cell clones revealed that the engagement of p40 molecules, using specific mAb, induced some degree of inhibition only on anti-Vβ (but not anti-Vδ or anti-CD3) mAb-induced cytotoxicity. On the other hand, the p40 molecule engagement prevented T cell proliferation induced by either anti-Vβ 8 or anti-Vδ 2 mAb. A similar inhibitory effect was found on the IL-2-induced NK cell proliferation. Taken together, our present findings suggest that p40 may play a role in the regulation of NK and T lymphocyte activation and proliferation. [ABSTRACT FROM AUTHOR]- Published
- 1997
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45. Physical and functional association of CD45 and CD3-TCR complex on CD1+ human thymocytes. Evidence that the engagement of CD45 molecules can prevent CD1+ thymocytes from apoptosis.
- Author
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Poggi, Alessandro, Pella, Nicoletta, Cantoni, Claudia, Zocchi, Maria Raffaella, and Moretta, Lorenzo
- Abstract
In this study the effects of CD45 engagement on CD3-TCR-driven stimulation of CD1
+ human immature thymocytes have been analyzed. Simultaneous cross-linking of CD45 and CD3 antigens on highly purified CD1+ thymocytes reduced the number of cells undergoing apoptosis after 16 h of In vitro culture. This cell population might represent immature thymocytes committed in vivo to die by programmed cell death (PCD). CD45 engagement could also increase the number of cycling CD1+ thymocytes; of note, the large majority (>95%) of dividing cells expressed the CD1 molecule at the cell surface, indicating that proliferating cells were actually represented by immature thymocytes. These data suggest that the CD45 molecule might play a role in the rescue of CD1 immature thymocytes from PCD during differentiation. Along this line, we found that activation of+ thymocytes via the CD3-TCR complex could be enhanced by CD45, both in terms of transcription and surface expression of IL-2R. These effects might be explained by the finding that the CD45 molecule (but not its isoforms CD45RO and RA) was physically associated with the CD3-TCR complex at the cell surface of CD1+ human thymocytes, as shown by co-precipitation and co-capping experiments. Finally, cross-linking of CD45 and CD3 antigens led to the expansion of CD3+ thymocytes co-expressing CD4 and CD8, indicating that simultaneous engagement of CD45 and CD3 molecules can block CD1+ cells at the double-positive (CD3+ CD4+ CD8+ ) differentiation stage. On the other hand, stimulation through CD3 resulted in the expansion of thymocytes showing a mature phenotype (CD3+ CD4+ or CD3+ CD8+ ). Altogether, these findings suggest that the CD45 molecule is involved both in early activation and in the regulation of CD1+ thymocyte differentiation. [ABSTRACT FROM AUTHOR]- Published
- 1996
- Full Text
- View/download PDF
46. Regulatory role of NKp44, NKp46, DNAM-1 and NKG2D receptors in the interaction between NK cells and trophoblast cells. Evidence for divergent functional profiles of decidual versus peripheral NK cells.
- Author
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Paola Vacca, Claudia Cantoni, Carola Prato, Ezio Fulcheri, Alessandro Moretta, Lorenzo Moretta, and Maria Cristina Mingari
- Subjects
KILLER cells ,FIRST trimester of pregnancy ,TROPHOBLAST ,CELL lines - Abstract
During the first trimester of pregnancy NK cells represent >50% of the lymphoid cells present in the human decidua where they reside in close contact with trophoblast cells. Because in decidual tissues NK cell activation and function may be induced by this interaction, we analyzed the cellular ligands recognized by activating NK receptors expressed on trophoblast cells. We show that these cells primarily express the NKp44 and DNAM-1 ligands and that interaction between these ligands and their corresponding receptors results in NK cell triggering. While activated peripheral blood NK (pNK) cells lysed the trophoblast cell lines JAR and JEG3, decidual NK (dNK) cells did not. On the other hand, they released VEGF, SDF-1, IP10 and large amounts of IL-8. Interaction with K562 target cells was exploited to induce optimal NK cell triggering, allowing a parallel, quantitative assessment of both cytolytic activity and cytokine production elicited by dNK cells. While dNK cells were unable to kill K562 even at high effector:target (E:T) ratios, they released large amounts of IL-8 also at low E:T ratios, a scenario compatible with dNK trophoblast cells interaction occurring within decidual tissues. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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- View/download PDF
47. Human NK cells directly recognize Mycobacterium bovis via TLR2 and acquire the ability to kill monocyte-derived DC.
- Author
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Emanuela Marcenaro, Bruna Ferranti, Michela Falco, Lorenzo Moretta, and Alessandro Moretta
- Subjects
CELLULAR mechanics ,KILLER cells ,BCG vaccines ,MYCOBACTERIUM - Abstract
NK cells are important players of the early innate defense against various pathogens. In this study, we investigated the interaction between human NK cells and Mycobacterium bovis [bacille Calmette–Guérin (BCG)] and we determined whether and how such an interaction might impact on NK cell activation, cytokine production and cytotoxicity. We show that highly purified NK cells, upon short-term co-culture with BCG, expressed activation markers including CD69 and CD25. Moreover, these NK cells released IFN-gamma and tumor necrosis factor-alpha and killed more efficiently different targets including monocyte-derived immature dendritic cell. All these functions were strongly up-regulated in the presence of exogenous IL-12. Although more efficient responses were detected in NK cell populations displaying an NCRbright phenotype, no direct evidence of an involvement of triggering NK receptors in BCG recognition could be obtained. On the other hand, anti-toll-like receptor (TLR)2 mAb inhibited NK cell responses to BCG, suggesting that NK cells may express a functional TLR2, which plays a role in their mechanism of direct BCG recognition. Taken together, these data suggest that BCG, by inducing simultaneous activation of NK and antigen-presenting cells via their ‘shared’ TLR2, can promote efficient bidirectional NK–dendritic cell interactions necessary for subsequent priming of Th1 responses. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
48. Heterogeneity of TLR3 mRNA transcripts and responsiveness to poly (I:C) in human NK cells derived from different donors.
- Author
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Simona Sivori, Michela Falco, Simona Carlomagno, Elisa Romeo, Lorenzo Moretta, and Alessandro Moretta
- Subjects
KILLER cells ,MESSENGER RNA ,CYTOKINES ,IMMUNOREGULATION - Abstract
TLR3 plays an important role in the activation of different cell types of the innate immune system. Previous studies indicated that human NK cells express TLR3 and that, upon stimulation by polyinosinic-polycytidylic acid [poly (I:C)], they release cytokines and up-regulate cytotoxicity. Here we show that NK cells display heterogeneous levels of TLR3 mRNA transcript. Analysis of NK cell clones did not reveal significant correlation between the levels of TLR3 mRNA transcripts and the expression of different surface NK receptors including killer Ig-like receptor and NKG2A. On the other hand, the level of TLR3 mRNA transcript detected in given clones correlated with the ability of these clones to respond to poly (I:C). Thus, clones displaying higher TLR3 mRNA transcripts were characterized by higher cytokine production and cytotoxicity. Moreover, the increased cytolytic activity induced by treatment with poly (I:C) does not depend on increment of the expression of activating NK receptors and co-receptors, adhesion molecules or perforin/granzyme, but correlates with higher cell responsiveness to NKp46 ligation. Remarkably, in the presence of poly (I:C), even NKp46dull NK cell clones become cytolytic when characterized by high levels of TLR3 transcript. Thus, our present study provides an useful tool for both a quantitative and qualitative analysis of TLR3 in NK cells and contributes to explain the heterogeneous responsiveness to poly (I:C) of NK cells derived from different individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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49. NK cells provide helper signal for CD8 T cells by inducing the expression of membrane-bound IL-15 on DCs.
- Author
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Barbara Morandi, Lorenzo Mortara, Paolo Carrega, Claudia Cantoni, Gregorio Costa, Roberto S. Accolla, Maria Cristina Mingari, Silvano Ferrini, Lorenzo Moretta, and Guido Ferlazzo
- Subjects
IMMUNOCOMPETENT cells ,CELL-mediated cytotoxicity ,LEUCOCYTES ,ANTIBODY-dependent cell cytotoxicity - Abstract
NK cell recognition of cells that do not express or express low amounts of MHC class I molecules results not only in direct killing of target cells but also in the generation of specific T cell responses consequent to the induction of dendritic cell (DC) activation. While IL-12 production by NK cell-activated DCs is generally thought to play a critical role, a similar DC-mediated NK cell help has been reported also in IL-12-knockout mice. Here, we show that human NK cells can induce on DC surface membrane, via IFN-γ secretion, the expression of high levels of IL-15. Remarkably, we show that DC expression of this membrane-bound form of IL-15, which is only partially associated with IL-15R molecules, is essential to promote specific CD8 T lymphocyte response in the absence of DC-derived IL-12. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
50. NKp44 expression, phylogenesis and function in non-human primate NK cells.
- Author
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Andrea De Maria, Elisabetta Ugolotti, Erik Rutjens, Stefania Mazza, Luana Radic, Alessandro Faravelli, Gerrit Koopman, Eddi Di Marco, Paola Costa, Barbara Ensoli, Aurelio Cafaro, Maria Cristina Mingari, Lorenzo Moretta, Jonathan Heeney, and Roberto Biassoni
- Subjects
KILLER cells ,GENETIC transcription ,MAMMALS ,GENE expression - Abstract
Molecular and functional characterization of the natural cytotoxicity receptor (NCR) NKp44 in species other than Homo sapiens has been elusive, so far. Here, we provide complete phenotypic, molecular and functional characterization for NKp44 triggering receptor on Pan troglodytes NK cells, the closest human relative, and the analysis of NKp44-genomic locus and transcription in Macaca fascicularis. Similar to H. sapiens, NKp44 expression is detectable on chimpanzee NK cells only upon activation. However, basal NKp44 transcription is 5-fold higher in chimpanzees with lower differential increases upon cell activation compared with humans. Upon activation, an overall 12-fold lower NKp44 gene expression is observed in P. troglodytes compared with H. sapiens NK cells with only a slight reduction in NKp44 surface expression. Functional analysis of ‘in vitro’ activated purified NK cells confirms the NKp44 triggering potential compared with other major NCRs. These findings suggest the presence of a post-transcriptional regulation that evolved differently in H. sapiens. Analysis of cynomolgus NKp44-genomic sequence and transcription pattern showed very low levels of transcription with occurrence of out-of-frame transcripts and no surface expression. The present comparative analysis suggests that NKp44-genomic organization appears during macaque speciation, with considerable evolution of its transcriptional and post-transcriptional tuning. Thus, NKp44 may represent an NCR being only recently emerged during speciation, acquiring functional relevance only in non-human primates closest to H. sapiens. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
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