Large-Scale HLA Tetramer Tracking of T Cells during Dengue Infection Reveals Broad Acute Activation and Differentiation into Two Memory Cell Fates

• Published in: Immunity (Cambridge, Mass.) Vol. 51; no. 6; pp. 1119 - 1135.e5
• Main Authors: Chng, Melissa Hui Yen, Lim, Mei Qiu, Rouers, Angeline, Becht, Etienne, Lee, Bernett, MacAry, Paul A., Lye, David Chien, Leo, Yee Sin, Chen, Jinmiao, Fink, Katja, Rivino, Laura, Newell, Evan W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-12-2019; Elsevier Limited
• Subjects: Adult; Antigens; B-Lymphocytes - immunology; Biomarkers; CD127; CD57; CD57 antigen; CD57 Antigens - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell activation; Cell differentiation; Cell Differentiation - immunology; Cell proliferation; Cell Proliferation - physiology; Chemokines; Convalescence; cytof; Cytokines; Cytometry; dengue; Dengue - immunology; Dengue fever; Dengue Virus - immunology; DENV; Differentiation; Disease control; Epitopes; Epitopes, T-Lymphocyte - immunology; Female; Histocompatibility antigen HLA; HLA Antigens - classification; HLA Antigens - immunology; Humans; IL-7R; Immunologic Memory - immunology; Immunological memory; Infections; Interleukin-7 Receptor alpha Subunit - metabolism; Killer Cells, Natural - immunology; Leukocytes; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Male; mass cytometry; memory; Memory cells; Middle Aged; Peptides; Plasma; Principal components analysis; Protein transport; Receptors; T cell; tetramer; Vaccination; Vaccines; Vector-borne diseases; Viral diseases; IL-7R; memory; T cell; DENV; CD127; mass cytometry; CD57; tetramer; dengue; cytof
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2019.10.007

T cells play important multifaceted roles during dengue infection, and understanding their responses is important for defining correlates of protective immunity and identifying effective vaccine antigens. Using mass cytometry and a highly multiplexed peptide-HLA (human leukocyte antigen) tetramer staining strategy, we probed T cells from dengue patients—a total of 430 dengue and control candidate epitopes—together with key markers of activation, trafficking, and differentiation. During acute disease, dengue-specific CD8+ T cells expressed a distinct profile of activation and trafficking receptors that distinguished them from non-dengue-specific T cells. During convalescence, dengue-specific T cells differentiated into two major cell fates, CD57+ CD127−-resembling terminally differentiated senescent memory cells and CD127+ CD57−-resembling proliferation-capable memory cells. Validation in an independent cohort showed that these subsets remained at elevated frequencies up to one year after infection. These analyses aid our understanding of the generation of T cell memory in dengue infection or vaccination.
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•Dengue infection causes broad activation and proliferation of many immune subsets•EBV- and influenza-specific T cells show no bystander activation during dengue infection•Dengue-specific T cells showed HLA-associated differences in activation markers•Dengue-specific T cells differentiated into two major cell fates
Understanding T cell responses to dengue infection is important for developing effective vaccines. Chng et al. used high-dimensional CyTOF profiling and peptide-HLA tetramer screening to track dengue-specific T cell activation and differentiation into memory cells in naturally infected patients. They found that dengue infection causes broad immune cell activation and that dengue-specific T cells differentiate into two major cell fates.