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1. Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance

Author

Ko, Emily R., Reller, Megan E., Tillekeratne, L. Gayani, Bodinayake, Champica K., Miller, Cameron, Burke, Thomas W., Henao, Ricardo, McClain, Micah T., Suchindran, Sunil, Nicholson, Bradly, Blatt, Adam, Petzold, Elizabeth, Tsalik, Ephraim L., Nagahawatte, Ajith, Devasiri, Vasantha, Rubach, Matthew P., Maro, Venance P., Lwezaula, Bingileki F., Kodikara-Arachichi, Wasantha, Kurukulasooriya, Ruvini, De Silva, Aruna D., Clark, Danielle V., Schully, Kevin L., Madut, Deng, Dumler, J. Stephen, Kato, Cecilia, Galloway, Renee, Crump, John A., Ginsburg, Geoffrey S., Minogue, Timothy D., and Woods, Christopher W.

Published
2023
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2. Cutting Edge: Transcriptional Profiling Reveals Multifunctional and Cytotoxic Antiviral Responses of Zika Virus–Specific CD8+ T Cells

Author

Grifoni, Alba, Costa-Ramos, Priscilla, Pham, John, Tian, Yuan, Rosales, Sandy L, Seumois, Grégory, Sidney, John, de Silva, Aruna D, Premkumar, Lakshmanane, Collins, Matthew H, Stone, Mars, Norris, Phillip J, Romero, Claudia ME, Durbin, Anna, Ricciardi, Michael J, Ledgerwood, Julie E, de Silva, Aravinda M, Busch, Michael, Peters, Bjoern, Vijayanand, Pandurangan, Harris, Eva, Falconar, Andrew K, Kallas, Esper, Weiskopf, Daniela, and Sette, Alessandro

Subjects
Prevention, Clinical Research, Biodefense, Emerging Infectious Diseases, Infectious Diseases, Vaccine Related, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Antigens, Viral, CD8-Positive T-Lymphocytes, Cells, Cultured, Cytotoxicity, Immunologic, Epitopes, T-Lymphocyte, Gene Expression Profiling, Granzymes, Humans, Immunoglobulins, Immunophenotyping, Interferon-gamma, Receptors, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha, Zika Virus, Zika Virus Infection, Immunology
Abstract

Zika virus (ZIKV) constitutes an increasing public health problem. Previous studies have shown that CD8+ T cells play an important role in ZIKV-specific protective immunity. We have previously defined antigenic targets of the ZIKV-specific CD8+ T cell response in humans. In this study, we characterized the quality and phenotypes of these responses by a combined use of flow cytometry and transcriptomic methods, using PBMCs from donors deriving from different geographical locations collected in the convalescent phase of infection. We show that ZIKV-specific CD8+ T cells are characterized by a polyfunctional IFN-γ signature with upregulation of TNF-α, TNF receptors, and related activation markers, such as CD69, as well as a cytotoxic signature characterized by strong upregulation of GZMB and CRTAM. The signature is stable and not influenced by previous dengue virus exposure, geographical location, or time of sample collection postinfection. To our knowledge, this work elucidates the first in-depth characterization of human CD8+ T cells responding to ZIKV infection.

Published
2018

3. Sequence-based HLA-A, B, C, DP, DQ, and DR typing of 714 adults from Colombo, Sri Lanka.

Author

Grifoni, Alba, Weiskopf, Daniela, Lindestam Arlehamn, Cecilia S, Angelo, Michael, Leary, Shay, Sidney, John, Frazier, April, Phillips, Elizabeth, Mallal, Simon, Mack, Steven J, Tippalagama, Rashmi, Goonewardana, Suraj, Premawansa, Sunil, Premawansa, Gayani, Wijewickrama, Ananda, De Silva, Aruna D, and Sette, Alessandro

Subjects
T-Lymphocytes, Animals, Humans, Mice, HLA-A Antigens, HLA-B Antigens, HLA-C Antigens, HLA-DP Antigens, HLA-DQ Antigens, HLA-DR Antigens, Histocompatibility Testing, Sequence Analysis, DNA, Gene Frequency, Genotype, Adult, Sri Lanka, Female, Male, Healthy Volunteers, Ethnicity, Colombo, Sri Lanka, HLA alleles, HLA typing, Moors, Sinhalese, Tamil, Genetics, Clinical Research, Good Health and Well Being, Colombo, Sri Lanka, Immunology
Abstract

DNA sequence-based typing at the HLA-A, -B, -C, -DPB1, -DQA1, -DQB1, and -DRB1 loci was performed on 714 healthy adult blood bank donors from Colombo, Sri Lanka, to characterize allele frequencies in support of studies on T cell immunity against pathogens, including Dengue virus. Deviations from Hardy Weinberg proportions were not detected at any locus. Several alleles were found in >30% of individuals, including the class II alleles DPB1 * 04:01, DPB1 * 02:01, DQB1 * 06:01 and DRB1 * 07:01, and the class I alleles A * 33:03 and A * 24:02. Genotype data will be available in the Allele Frequencies Net Database.

Published
2018

4. Prior Dengue Virus Exposure Shapes T Cell Immunity to Zika Virus in Humans

Author

Grifoni, Alba, Pham, John, Sidney, John, O'Rourke, Patrick H, Paul, Sinu, Peters, Bjoern, Martini, Sheridan R, de Silva, Aruna D, Ricciardi, Michael J, Magnani, Diogo M, Silveira, Cassia GT, Maestri, Alvino, Costa, Priscilla R, de-Oliveira-Pinto, Luzia Maria, de Azeredo, Elzinandes Leal, Damasco, Paulo Vieira, Phillips, Elizabeth, Mallal, Simon, de Silva, Aravinda M, Collins, Matthew, Durbin, Anna, Diehl, Sean A, Cerpas, Cristhiam, Balmaseda, Angel, Kuan, Guillermina, Coloma, Josefina, Harris, Eva, Crowe, James E, Stone, Mars, Norris, Phillip J, Busch, Michael, Vivanco-Cid, Hector, Cox, Josephine, Graham, Barney S, Ledgerwood, Julie E, Turtle, Lance, Solomon, Tom, Kallas, Esper G, Watkins, David I, Weiskopf, Daniela, and Sette, Alessandro

Subjects
Vaccine Related, Infectious Diseases, Immunization, Emerging Infectious Diseases, Biodefense, Prevention, Vector-Borne Diseases, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Infection, Inflammatory and immune system, Good Health and Well Being, Adolescent, Adult, Aged, Child, Child, Preschool, Cohort Studies, Cross Reactions, Dengue Vaccines, Dengue Virus, Epitopes, T-Lymphocyte, Female, Humans, Male, Middle Aged, T-Lymphocytes, Vaccines, Attenuated, Young Adult, Zika Virus, Zika Virus Infection, ZIKV, DENV, T cells, heterologous immunity, cross-reactivity, immunodominance, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology
Abstract

While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here, we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether preexisting dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with tetravalent dengue attenuated vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors but declines in DENV-preexposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive donors. Finally, we discovered that ZIKV structural proteins (E, prM, and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins.IMPORTANCE The issue of potential ZIKV and DENV cross-reactivity and how preexisting DENV T cell immunity modulates Zika T cell responses is of great relevance, as the two viruses often cocirculate and Zika virus has been spreading in geographical regions where DENV is endemic or hyperendemic. Our data show that memory T cell responses elicited by prior infection with DENV recognize ZIKV-derived peptides and that DENV exposure prior to ZIKV infection influences the timing, magnitude, and quality of the T cell response. Additionally, we show that ZIKV-specific responses target different proteins than DENV-specific responses, pointing toward important implications for vaccine design against this global threat.

Published
2017

5. An Integrated Workflow To Assess Technical and Biological Variability of Cell Population Frequencies in Human Peripheral Blood by Flow Cytometry

Author

Burel, Julie G, Qian, Yu, Lindestam Arlehamn, Cecilia, Weiskopf, Daniela, Zapardiel-Gonzalo, Jose, Taplitz, Randy, Gilman, Robert H, Saito, Mayuko, de Silva, Aruna D, Vijayanand, Pandurangan, Scheuermann, Richard H, Sette, Alessandro, and Peters, Bjoern

Subjects
Clinical Research, Good Health and Well Being, Adult, Age Factors, CD4-Positive T-Lymphocytes, CD56 Antigen, Cell Count, Female, Flow Cytometry, Humans, Immunophenotyping, Latent Tuberculosis, Leukocytes, Mononuclear, Male, Sex Factors, T-Lymphocyte Subsets, Workflow, Immunology
Abstract

In the context of large-scale human system immunology studies, controlling for technical and biological variability is crucial to ensure that experimental data support research conclusions. In this study, we report on a universal workflow to evaluate both technical and biological variation in multiparameter flow cytometry, applied to the development of a 10-color panel to identify all major cell populations and T cell subsets in cryopreserved PBMC. Replicate runs from a control donation and comparison of different gating strategies assessed the technical variability associated with each cell population and permitted the calculation of a quality control score. Applying our panel to a large collection of PBMC samples, we found that most cell populations showed low intraindividual variability over time. In contrast, certain subpopulations such as CD56 T cells and Temra CD4 T cells were associated with high interindividual variability. Age but not gender had a significant effect on the frequency of several populations, with a drastic decrease in naive T cells observed in older donors. Ethnicity also influenced a significant proportion of immune cell population frequencies, emphasizing the need to account for these covariates in immune profiling studies. We also exemplify the usefulness of our workflow by identifying a novel cell-subset signature of latent tuberculosis infection. Thus, our study provides a universal workflow to establish and evaluate any flow cytometry panel in systems immunology studies.

Published
2017

7. Nonclonal Burkholderia pseudomallei Population in Melioidosis Case Cluster, Sri Lanka

Author

Jayasinghearachchi, Himali S., Francis, Vaithehi R., Sathkumara, Harindra D., Krishnananthasivam, Shivankari, Masakorala, Jayanthi, Muthugama, Thilini, De Silva, Aruna D., and Corea, Enoka M.

Subjects
Burkholderia pseudomallei -- Identification and classification -- Genetic aspects, Pseudomonas infections -- Causes of, Health
Abstract

Melioidosis, an emerging tropical infection caused by the soil bacterium Burkholderia pseudomallei, is found most commonly in northern Australia and the tropical countries of Southeast Asia. Melioidosis is endemic in [...]

Published
2021
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9. Dengue-specific [CD8.sup.+] T cell subsets display specialized transcriptomic and TCR profiles

Author

Tian, Yuan, Babor, Mariana, Lane, Jerome, Seumois, Gregory, Liang, Shu, Goonawardhana, N.D. Suraj, De Silva, Aruna D., Phillips, Elizabeth J., Mallal, Simon A., Antunes, Ricardo da Silva, Grifoni, Alba, Vijayanand, Pandurangan, Weiskopf, Daniela, Peters, Bjoern, and Sette, Alessandro

Subjects
Dengue virus -- Genetic aspects -- Risk factors -- Prevention, T cells -- Research, Transcription (Genetics) -- Research, Viral vaccines -- Usage, Vaccines, Benchmarking, Antigens, Dengue fever, Antigenic determinants, Gene expression, Genes, Genetic research, Health care industry
Abstract

Accumulating evidence demonstrates that [CD8.sup.+] T cells contribute to protection from severe dengue virus (DENV) disease and vaccine efficacy. Nevertheless, molecular programs associated with DENV-specific [CD8.sup.+] T cell subsets have not been defined. Here, we studied the transcriptomic profiles of human DENV-specific [CD8.sup.+] T cells isolated after stimulation with DENV epitopes from donors who had been infected with DENV multiple times and would therefore be expected to have significant levels of adaptive immunity. We found that DENV-specific [CD8.sup.+] T cells mainly consisted of effector memory subsets, namely [CD45RA.sup.-][CCR7.sup.-] effector memory (Tem) and [CD45RA.sup.+][CCR7.sup.-] effector memory re-expressing CD45RA (Temra) cells, which enacted specific gene expression profiles upon stimulation with cognate antigens. DENV-specific [CD8.sup.+] T cell subsets in general, and Temra cells in particular, were fully activated and polyfunctional, yet associated with relatively narrow transcriptional responses. Furthermore, we found that DENV-specific [CD8.sup.+] Tem and Temra cells showed some unique T cell receptor features in terms of overlap and variable (V) gene usage. This study provides a transcriptomic definition of DENV-specific activated human [CD8.sup.+] T cell subsets and defines a benchmark profile that vaccine-specific responses could aim to reproduce., Introduction Dengue virus (DENV) infection is a serious public health problem in tropical and subtropical areas, and it is estimated that approximately 390 million people are infected yearly (1). DENV [...]

Published
2019
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16. Correction: Outcomes among children and adults at risk of severe dengue in Sri Lanka: Opportunity for outpatient case management in countries with high disease burden

Author

Bodinayake, Champica K., primary, Nagahawatte, Ajith DeS, additional, Devasiri, Vasantha, additional, Dahanayake, Niroshana J., additional, Wijayaratne, Gaya B., additional, Weerasinghe, Nayani P., additional, Premamali, Madureka, additional, Sheng, Tianchen, additional, Nicholson, Bradley P., additional, Ubeysekera, Harshanie A., additional, Kurukulasooriya, Ruvini MP, additional, de Silva, Aruna D., additional, Østbye, Truls, additional, Woods, Christopher W., additional, and Tillekeratne, L. Gayani, additional

Published
2022
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17. Transcriptomics of Acute DENV-Specific CD8+ T Cells Does Not Support Qualitative Differences as Drivers of Disease Severity

Author

Grifoni, Alba, primary, Voic, Hannah, additional, Yu, Esther Dawen, additional, Mateus, Jose, additional, Yan Fung, Kai Mei, additional, Wang, Alice, additional, Seumois, Grégory, additional, De Silva, Aruna D., additional, Tennekon, Rashika, additional, Premawansa, Sunil, additional, Premawansa, Gayani, additional, Tippalagama, Rashmi, additional, Wijewickrama, Ananda, additional, Chawla, Ashu, additional, Greenbaum, Jason, additional, Peters, Bjoern, additional, Pandurangan, Vijayanand, additional, Weiskopf, Daniela, additional, and Sette, Alessandro, additional

Published
2022
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18. Outcomes among children and adults at risk of severe dengue in Sri Lanka: Opportunity for outpatient case management in countries with high disease burden

Author

Bodinayake, Champica K., primary, Nagahawatte, Ajith DeS, additional, Devasiri, Vasantha, additional, Dahanayake, Niroshana J., additional, Wijayaratne, Gaya B., additional, Weerasinghe, Nayani P., additional, Premamali, Madureka, additional, Sheng, Tianchen, additional, Nicholson, Bradley P., additional, Ubeysekera, Harshanie A., additional, Kurukulasooriya, Ruvini MP, additional, de Silva, Aruna D., additional, Østbye, Truls, additional, Woods, Christopher W., additional, and Tillekeratne, L Gayani, additional

Published
2021
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20. Transcriptomics of acute DENV-specific CD8+ T cells does not support qualitative differences as drivers of disease severity

Author

Grifoni, Alba, primary, Voic, Hannah, additional, Mateus, Jose, additional, Fung, Kai Mei Yan, additional, Wang, Alice, additional, Seumois, Grégory, additional, De Silva, Aruna D., additional, Tennekon, Rashika, additional, Premawansa, Sunil, additional, Premawansa, Gayani, additional, Tippalgama, Rashmi, additional, Wijewickrama, Ananda, additional, Chawla, Ashu, additional, Greenbaum, Jason, additional, Peters, Bjoern, additional, Pandagrundan, Vijayanand, additional, Weiskopf, Daniela, additional, and Sette, Alessandro, additional

Published
2021
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21. Pre-existing T Cell Memory against Zika Virus

Author

Schouest, Blake, primary, Grifoni, Alba, additional, Pham, John, additional, Mateus, Jose, additional, Sydney, John, additional, Brien, James D., additional, De Silva, Aruna D., additional, Balmaseda, Angel, additional, Harris, Eva, additional, Sette, Alessandro, additional, and Weiskopf, Daniela, additional

Published
2021
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22. T cell responses induced by attenuated flavivirus vaccination are specific and show limited cross-reactivity with other flavivirus species

Author

Grifoni, Alba, Voic, Hannah, Dhanda, Sandeep Kumar, Kidd, Conner K., Brien, James D., Buus, Søren, Stryhn, Anette, Durbin, Anna P., Whitehead, Stephen, Diehl, Sean A., De Silva, Aruna D., Balmaseda, Angel, Harris, Eva, Weiskopf, Daniela, Sette, Alessandro, Grifoni, Alba, Voic, Hannah, Dhanda, Sandeep Kumar, Kidd, Conner K., Brien, James D., Buus, Søren, Stryhn, Anette, Durbin, Anna P., Whitehead, Stephen, Diehl, Sean A., De Silva, Aruna D., Balmaseda, Angel, Harris, Eva, Weiskopf, Daniela, and Sette, Alessandro

Abstract

Members of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. In this study, we tested pools of epitopes derived from dengue (DENV), Zika (ZIKV), Japanese encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by intracellular cytokine staining (ICS) using peripheral blood mononuclear cells (PBMCs) of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccine. CD8 T cell responses recognized epitopes from multiple flaviviruses; however, the magnitude of cross-reactive responses was consistently severalfold lower than those to the autologous epitope pools and was associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-Term T cell lines (TCL) representing 29 different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees induced CD8 and CD4 T cells that cross-reacted within the DENV serocomplex but were consistently associated with > 100-fold-lower antigen sensitivity for most other flaviviruses, with no cross-recognition of YFV-derived peptides. CD8 and CD4 TCL from YF17D vaccinees were associated with very limited cross-reactivity with any other flaviviruses and in five out of eight cases > 1,000-foldlower antigen sensitivity. Overall, our data suggest limited cross-reactivity for both CD4 and CD8 T cell responses between flaviviruses and have implications for understanding immunity elicited by natural infection and strategies to develop live attenuated vaccines against flaviviral species.

Published
2020

23. T Cell Responses Induced by Attenuated Flavivirus Vaccination Are Specific and Show Limited Cross-Reactivity with Other Flavivirus Species

Author

Grifoni, Alba, primary, Voic, Hannah, additional, Dhanda, Sandeep Kumar, additional, Kidd, Conner K., additional, Brien, James D., additional, Buus, Søren, additional, Stryhn, Anette, additional, Durbin, Anna P., additional, Whitehead, Stephen, additional, Diehl, Sean A., additional, De Silva, Aruna D., additional, Balmaseda, Angel, additional, Harris, Eva, additional, Weiskopf, Daniela, additional, and Sette, Alessandro, additional

Published
2020
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24. Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-producing CD4 T Cells and Their Association with Dengue Disease

Author

Tian, Yuan, primary, Seumois, Grégory, additional, De-Oliveira-Pinto, Luzia M., additional, Mateus, Jose, additional, Herrera-de la Mata, Sara, additional, Kim, Cheryl, additional, Hinz, Denise, additional, Goonawardhana, N.D. Suraj, additional, de Silva, Aruna D., additional, Premawansa, Sunil, additional, Premawansa, Gayani, additional, Wijewickrama, Ananda, additional, Balmaseda, Angel, additional, Grifoni, Alba, additional, Vijayanand, Pandurangan, additional, Harris, Eva, additional, Peters, Bjoern, additional, Sette, Alessandro, additional, and Weiskopf, Daniela, additional

Published
2019
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25. Characterization of Magnitude and Antigen Specificity of HLA-DP, DQ, and DRB3/4/5 Restricted DENV-Specific CD4+ T Cell Responses

Author

Grifoni, Alba, primary, Moore, Eugene, additional, Voic, Hannah, additional, Sidney, John, additional, Phillips, Elizabeth, additional, Jadi, Ramesh, additional, Mallal, Simon, additional, De Silva, Aruna D., additional, De Silva, Aravinda M., additional, Peters, Bjoern, additional, Weiskopf, Daniela, additional, and Sette, Alessandro, additional

Published
2019
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26. CD4 T cell transcriptomics reveal novel diagnostic and mechanistic immune signatures of tuberculosis

Author

Burel, Julie G, primary, Lindestam Arlehamn, Cecilia S, additional, Pomaznoy, Mikhail, additional, Seumois, Gregory, additional, Greenbaum, Jason A, additional, Vidanagama, Dhammika, additional, Gunasena, Bandu, additional, Tippalagama, Rashmi, additional, de Silva, Aruna D, additional, Taplitz, Randy, additional, Vijayanand, Pandurangan, additional, Sette, Alessandro, additional, and Peters, Bjoern, additional

Published
2019
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28. Characterization of HLA-DP and DQ restricted dengue virus-specific CD4+T cell responses reveals lower magnitude responses associated with a differential pattern of immunodominance as compared to DR restricted responses

Author

Weiskopf, Daniela, primary, Grifoni, Alba, additional, Angelo, Michael, additional, Moore, Eugene, additional, Sidney, John, additional, Phillips, Elizabeth J, additional, Mallal, Simon Alexander, additional, de Silva, Aruna D, additional, Peters, Bjoern, additional, and Sette, Alessandro, additional

Published
2019
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29. Molecular Signatures of IL-10/IFN-γ Co-Producing CD4 T Cells During Acute Dengue Virus Infection

Author

Tian, Yuan, primary, Seumois, Gregory, additional, de la Mata, Sara Herrera, additional, Goonawardhana, Suraj, additional, de Silva, Aruna D, additional, Premawansa, Sunil, additional, Premawansa, Gayani, additional, Wijewickrama, Ananda, additional, Grifoni, Alba, additional, Vijayanand, Pandurangan, additional, Peters, Bjoern, additional, Weiskopf, Daniela, additional, and Sette, Alessandro, additional

Published
2019
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30. Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-Producing CD4 T Cells and Their Association with Severe Dengue Disease

Author

Tian, Yuan, primary, Seumois, Grégory, additional, De-Oliveira-Pinto, Luzia M., additional, Herrera-de la Mata, Sara, additional, Kim, Cheryl, additional, Hinz, Denise, additional, Goonawardhana, N.D. Suraj, additional, de Silva, Aruna D., additional, Premawansa, Sunil, additional, Premawansa, Gayani, additional, Wijewickrama, Ananda, additional, Balmaseda, Angel, additional, Grifoni, Alba, additional, Vijayanand, Pandurangan, additional, Harris, Eva, additional, Peters, Bjoern, additional, Sette, Alessandro, additional, and Weiskopf, Daniela, additional

Published
2019
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31. Dengue type 1 viruses circulating in humans are highly infectious and poorly neutralized by human antibodies

Author

Raut, Rajendra, primary, Corbett, Kizzmekia S., additional, Tennekoon, Rashika N., additional, Premawansa, Sunil, additional, Wijewickrama, Ananda, additional, Premawansa, Gayani, additional, Mieczkowski, Piotr, additional, Rückert, Claudia, additional, Ebel, Gregory D., additional, De Silva, Aruna D., additional, and de Silva, Aravinda M., additional

Published
2018
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32. Immuno-proteomic interrogation of dengue infection reveals novel HLA haplotype-specific MHC-I antigens

Author

Swaminathan, Kavya, primary, Olsson, Niclas, additional, Lund, Peder J., additional, Marceau, Caleb D., additional, Wagar, Lisa E., additional, Tian, Yuan, additional, Sidney, John, additional, Weiskopf, Daniela, additional, Majzoub, Karim, additional, de Silva, Aruna D., additional, Harris, Eva, additional, Davis, Mark M., additional, Sette, Alessandro, additional, Carette, Jan E., additional, and Elias, Joshua E., additional

Published
2018
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33. Development of Envelope Protein Antigens To Serologically Differentiate Zika Virus Infection from Dengue Virus Infection

Author

Premkumar, Lakshmanane, primary, Collins, Matthew, additional, Graham, Stephen, additional, Liou, Guei-Jiun Alice, additional, Lopez, Cesar A., additional, Jadi, Ramesh, additional, Balmaseda, Angel, additional, Brackbill, James A., additional, Dietze, Reynaldo, additional, Camacho, Erwin, additional, De Silva, Aruna D., additional, Giuberti, Camila, additional, dos Reis, Helena Lucia, additional, Singh, Tulika, additional, Heimsath, Holly, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Osorio, Jorge E., additional, Permar, Sallie R., additional, Miley, Michel J., additional, Lazear, Helen M., additional, Harris, Eva, additional, and de Silva, Aravinda M., additional

Published
2018
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34. Evaluation of the WHO 2009 classification for diagnosis of acute dengue in a large cohort of adults and children in Sri Lanka during a dengue-1 epidemic

Author

Bodinayake, Champica K., primary, Tillekeratne, L. Gayani, additional, Nagahawatte, Ajith, additional, Devasiri, Vasantha, additional, Kodikara Arachchi, Wasantha, additional, Strouse, John J., additional, Sessions, October M., additional, Kurukulasooriya, Ruvini, additional, Uehara, Anna, additional, Howe, Shiqin, additional, Ong, Xin Mei, additional, Tan, Sharon, additional, Chow, Angelia, additional, Tummalapalli, Praveen, additional, De Silva, Aruna D., additional, Østbye, Truls, additional, Woods, Christopher W., additional, Gubler, Duane J., additional, and Reller, Megan E., additional

Published
2018
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35. Precursors of human CD4 + cytotoxic T lymphocytes identified by single-cell transcriptome analysis

Author

Patil, Veena S., primary, Madrigal, Ariel, additional, Schmiedel, Benjamin J., additional, Clarke, James, additional, O’Rourke, Patrick, additional, de Silva, Aruna D., additional, Harris, Eva, additional, Peters, Bjoern, additional, Seumois, Gregory, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, and Vijayanand, Pandurangan, additional

Published
2018
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36. Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA

Author

Tian, Yuan, primary, Babor, Mariana, additional, Lane, Jerome, additional, Schulten, Veronique, additional, Patil, Veena S., additional, Seumois, Grégory, additional, Rosales, Sandy L., additional, Fu, Zheng, additional, Picarda, Gaelle, additional, Burel, Julie, additional, Zapardiel-Gonzalo, Jose, additional, Tennekoon, Rashika N., additional, De Silva, Aruna D., additional, Premawansa, Sunil, additional, Premawansa, Gayani, additional, Wijewickrama, Ananda, additional, Greenbaum, Jason A., additional, Vijayanand, Pandurangan, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, and Peters, Bjoern, additional

Published
2017
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37. Global Assessment of Dengue Virus-Specific CD4+ T Cell Responses in Dengue-Endemic Areas

Author

Grifoni, Alba, primary, Angelo, Michael A., additional, Lopez, Benjamin, additional, O’Rourke, Patrick H., additional, Sidney, John, additional, Cerpas, Cristhiam, additional, Balmaseda, Angel, additional, Silveira, Cassia G. T., additional, Maestri, Alvino, additional, Costa, Priscilla R., additional, Durbin, Anna P., additional, Diehl, Sean A., additional, Phillips, Elizabeth, additional, Mallal, Simon, additional, De Silva, Aruna D., additional, Nchinda, Godwin, additional, Nkenfou, Celine, additional, Collins, Matthew H., additional, de Silva, Aravinda M., additional, Lim, Mei Qiu, additional, Macary, Paul A., additional, Tatullo, Filippo, additional, Solomon, Tom, additional, Satchidanandam, Vijaya, additional, Desai, Anita, additional, Ravi, Vasanthapram, additional, Coloma, Josefina, additional, Turtle, Lance, additional, Rivino, Laura, additional, Kallas, Esper G., additional, Peters, Bjoern, additional, Harris, Eva, additional, Sette, Alessandro, additional, and Weiskopf, Daniela, additional

Published
2017
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38. The CD4 T cell response in acute infection with dengue virus

Author

Weiskopf, Daniela, primary, de-Oliveira-Pinto, Luzia M, additional, Tian, Yuan, additional, de Silva, Aruna D, additional, Seumois, Gregory, additional, Vijayanand, Pandurangan, additional, Premawansa, Sunil, additional, Premawansa, Gayani, additional, Wijewickrama, Ananda, additional, Peters, Bjoern, additional, and Sette, Alessandro, additional

Published
2017
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39. Cellular immunity patterns of rDEN2Δ30 (Tonga/74) support its suitability as a human DENV challenge strain.

Author

Grifoni, Alba, primary, Angelo, Michael, additional, Sidney, John, additional, Paul, Sinu, additional, Peters, Bjoern, additional, de Silva, Aruna D, additional, Phillips, Elizabeth J, additional, Mallal, Simon Alexander, additional, Diehl, Sean A, additional, Botten, Jason, additional, Boyson, Jonathan E, additional, Kirkpatrick, Beth D, additional, Whitehead, Stephen S, additional, Durbin, Anna, additional, Sette, Alessandro, additional, and Weiskopf, Daniela, additional

Published
2017
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40. Patterns of Cellular Immunity Associated with Experimental Infection with rDEN2Δ30 (Tonga/74) Support Its Suitability as a Human Dengue Virus Challenge Strain

Author

Grifoni, Alba, primary, Angelo, Michael, additional, Sidney, John, additional, Paul, Sinu, additional, Peters, Bjoern, additional, de Silva, Aruna D., additional, Phillips, Elizabeth, additional, Mallal, Simon, additional, Diehl, Sean A., additional, Botten, Jason, additional, Boyson, Jonathan, additional, Kirkpatrick, Beth D., additional, Whitehead, Stephen S., additional, Durbin, Anna P., additional, Sette, Alessandro, additional, and Weiskopf, Daniela, additional

Published
2017
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41. Human CD4 + T Cell Responses to an Attenuated Tetravalent Dengue Vaccine Parallel Those Induced by Natural Infection in Magnitude, HLA Restriction, and Antigen Specificity

Author

Angelo, Michael A., primary, Grifoni, Alba, additional, O'Rourke, Patrick H., additional, Sidney, John, additional, Paul, Sinu, additional, Peters, Bjoern, additional, de Silva, Aruna D., additional, Phillips, Elizabeth, additional, Mallal, Simon, additional, Diehl, Sean A., additional, Kirkpatrick, Beth D., additional, Whitehead, Stephen S., additional, Durbin, Anna P., additional, Sette, Alessandro, additional, and Weiskopf, Daniela, additional

Published
2017
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42. Emergence of Epidemic Dengue-1 Virus in the Southern Province of Sri Lanka

Author

Bodinayake, Champica K., primary, Tillekeratne, L. Gayani, additional, Nagahawatte, Ajith, additional, Devasiri, Vasantha, additional, Kodikara Arachichi, Wasantha, additional, Strouse, John J., additional, Sessions, October M., additional, Kurukulasooriya, Ruvini, additional, Uehara, Anna, additional, Howe, Shiqin, additional, Ong, Xin Mei, additional, Tan, Sharon, additional, Chow, Angelia, additional, Tummalapalli, Praveen, additional, De Silva, Aruna D., additional, Østbye, Truls, additional, Woods, Christopher W., additional, Gubler, Duane J., additional, and Reller, Megan E., additional

Published
2016
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43. HLA-DRB1 Alleles Are Associated With Different Magnitudes of Dengue Virus–Specific CD4+T-Cell Responses

Author

Weiskopf, Daniela, primary, Angelo, Michael A., additional, Grifoni, Alba, additional, O'Rourke, Patrick H., additional, Sidney, John, additional, Paul, Sinu, additional, De Silva, Aruna D., additional, Phillips, Elizabeth, additional, Mallal, Simon, additional, Premawansa, Sunil, additional, Premawansa, Gayani, additional, Wijewickrama, Ananda, additional, Peters, Bjoern, additional, and Sette, Alessandro, additional

Published
2016
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45. Immunodominant Dengue Virus-Specific CD8 + T Cell Responses Are Associated with a Memory PD-1 + Phenotype

Author

de Alwis, Ruklanthi, primary, Bangs, Derek J., additional, Angelo, Michael A., additional, Cerpas, Cristhiam, additional, Fernando, Anira, additional, Sidney, John, additional, Peters, Bjoern, additional, Gresh, Lionel, additional, Balmaseda, Angel, additional, de Silva, Aruna D., additional, Harris, Eva, additional, Sette, Alessandro, additional, and Weiskopf, Daniela, additional

Published
2016
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46. Precursors of human CD4+ cytotoxic T lymphocytes identified by single-cell transcriptome analysis.

Author

Patil, Veena S., Madrigal, Ariel, Schmiedel, Benjamin J., Clarke, James, O’Rourke, Patrick, de Silva, Aruna D., Harris, Eva, Peters, Bjoern, Seumois, Gregory, Weiskopf, Daniela, Sette, Alessandro, and Vijayanand, Pandurangan

Abstract

CD4+ cytotoxic T lymphocytes (CD4-CTLs) have been reported to play a protective role in several viral infections. However, little is known in humans about the biology of CD4-CTL generation, their functional properties, and heterogeneity, especially in relation to other well-described CD4+ memory T cell subsets. We performed single-cell RNA sequencing in more than 9000 cells to unravel CD4-CTL heterogeneity, transcriptional profile, and clonality in humans. Single-cell differential gene expression analysis revealed a spectrum of known transcripts, including several linked to cytotoxic and costimulatory function that are expressed at higher levels in the TEMRA (effector memory T cells expressing CD45RA) subset, which is highly enriched for CD4-CTLs, compared with CD4+ T cells in the central memory (TCM) and effector memory (TEM) subsets. Simultaneous T cell antigen receptor (TCR) analysis in single cells and bulk subsets revealed that CD4-TEMRA cells show marked clonal expansion compared with TCM and TEM cells and that most of CD4-TEMRA were dengue virus (DENV)–specific in donors with previous DENV infection. The profile of CD4-TEMRA was highly heterogeneous across donors, with four distinct clusters identified by the single-cell analysis. We identified distinct clusters of CD4-CTL effector and precursor cells in the TEMRA subset; the precursor cells shared TCR clonotypes with CD4-CTL effectors and were distinguished by high expression of the interleukin-7 receptor. Our identification of a CD4-CTL precursor population may allow further investigation of how CD4-CTLs arise in humans and, thus, could provide insights into the mechanisms that may be used to generate durable and effective CD4-CTL immunity. [ABSTRACT FROM AUTHOR]

Published
2018
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48. Human CD8+T-Cell Responses Against the 4 Dengue Virus Serotypes Are Associated With Distinct Patterns of Protein Targets

Author

Weiskopf, Daniela, primary, Cerpas, Cristhiam, additional, Angelo, Michael A., additional, Bangs, Derek J., additional, Sidney, John, additional, Paul, Sinu, additional, Peters, Bjoern, additional, Sanches, Françoise P., additional, Silvera, Cassia G. T., additional, Costa, Priscilla R., additional, Kallas, Esper G., additional, Gresh, Lionel, additional, de Silva, Aruna D., additional, Balmaseda, Angel, additional, Harris, Eva, additional, and Sette, Alessandro, additional

Published
2015
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49. The Human CD8 + T Cell Responses Induced by a Live Attenuated Tetravalent Dengue Vaccine Are Directed against Highly Conserved Epitopes

Author

Weiskopf, Daniela, primary, Angelo, Michael A., additional, Bangs, Derek J., additional, Sidney, John, additional, Paul, Sinu, additional, Peters, Bjoern, additional, de Silva, Aruna D., additional, Lindow, Janet C., additional, Diehl, Sean A., additional, Whitehead, Stephen, additional, Durbin, Anna, additional, Kirkpatrick, Beth, additional, and Sette, Alessandro, additional

Published
2015
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50. Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA.

Author

Yuan Tian, Babor, Mariana, Lane, Jerome, Schulten, Veronique, Patil, Veena S., Seumois, Grégory, Rosales, Sandy L., Burel, Julie, Zapardiel-Gonzalo, Jose, Vijayanand, Pandurangan, Weiskopf, Daniela, Sette, Alessandro, Peters, Bjoern, Tennekoon, Rashika N., De Silva, Aruna D., Zheng Fu, Greenbaum, Jason A., Picarda, Gaelle, Premawansa, Sunil, and Premawansa, Gayani

Subjects
PHENOTYPES, T cells, CLONE cells, CD4 antigen, DENGUE viruses
Abstract

The expression of CD45RA is generally associated with naive T cells. However, a subset of effector memory T cells re-expresses CD45RA (termed TEMRA) after antigenic stimulation with unknown molecular characteristics and functions. CD4 TEMRA cells have been implicated in protective immunity against pathogens such as dengue virus (DENV). Here we show that not only the frequency but also the phenotype of CD4 TEMRA cells are heterogeneous between individuals. These cells can be subdivided into two major subsets based on the expression of the adhesion G protein-coupled receptor GPR56, and GPR56+ TEMRA cells display a transcriptional and proteomic program with cytotoxic features that is distinct from effector memory T cells. Moreover, GPR56+ TEMRA cells have higher levels of clonal expansion and contain the majority of virus-specific TEMRA cells. Overall, this study reveals the heterogeneity of CD4 TEMRA cells and provides insights into T-cell responses against DENV and other viral pathogens. [ABSTRACT FROM AUTHOR]

Published
2017
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