La Jolla Institute for Immunology - Center for Infectious Disease and Vaccine Research; La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery
Columbia University - Department of Microbiology and Immunology; Columbia University - Columbia Center for Translational Immunology; Columbia University, Columbia University Medical Center, Department of Surgery
The persistence of anti-viral immunity throughout the human body is essential for protection, and exhibits profound heterogeneity across individuals. Here, we elucidate the factors that shape the maintenance and function of anti-viral T cell immunity by comprehensive profiling of virus-specific T cells across blood, lymphoid organs, and mucosal tissues of organ donors. We used flow cytometry, T cell receptor analysis, single-cell transcriptomics, and cytokine analysis to profile virus-specific CD8+ T cells recognizing ubiquitous pathogens influenza and cytomegalovirus. Our results reveal that virus specificity determines the overall magnitude, tissue distribution, differentiation, and clonal repertoire of virus-specific T cells. Age and sex influence T cell differentiation and dissemination in tissues, while T cell tissue residence and functionality is highly correlated with the site. Together, our results demonstrate how the covariates of virus, tissue, age, and sex impact the anti-viral immune response, important for targeting, monitoring, and predicting immune responses to existing and emerging viruses.
Keywords: anti-viral immunity, T cells, tissue immunity, human immunology, cytomegalovirus, influenza, immunological memory
Poon, Maya M.L. and Byington, Eve and Meng, Wenzhao and Kubota, Masaru and Matsumoto, Rei and Grifoni, Alba and Weiskopf, Daniela and Dogra, Pranay and Lam, Nora and Szabo, Peter A. and Ural, Basak Burcu and Wells, Steven B. and Rosenfeld, Aaron M. and Brusko, Maigan A. and Brusko, Todd M. and Connors, Thomas J. and Sette, Alessandro and Sims, Peter A. and Luning Prak, Eline T. and Shen, Yufeng and Farber, Donna, Heterogeneity of Human Anti-Viral Immunity Shaped by Virus, Tissue, Age, and Sex. Available at SSRN: https://ssrn.com/abstract=3881346 or http://dx.doi.org/10.2139/ssrn.3881346
This version of the paper has not been formally peer reviewed.
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