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Heterogeneity of Human Anti-Viral Immunity Shaped by Virus, Tissue, Age, and Sex

67 Pages Posted: 6 Jul 2021 Publication Status: Review Complete

See all articles by Maya M.L. Poon

Maya M.L. Poon

Columbia University - Department of Microbiology and Immunology

Eve Byington

Columbia University - Department of Systems Biology

Wenzhao Meng

University of Pennsylvania - Department of Pathology and Laboratory Medicine

Masaru Kubota

Columbia University - Department of Surgery

Rei Matsumoto

Columbia University - Department of Surgery

Alba Grifoni

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Daniela Weiskopf

La Jolla Institute for Immunology - Center for Infectious Disease and Vaccine Research; La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Pranay Dogra

Columbia University - Department of Microbiology and Immunology

Nora Lam

Columbia University Irving Medical Center - Department of Pathology and Cell Biology

Peter A. Szabo

Columbia University - Department of Microbiology and Immunology

Basak Burcu Ural

Columbia University - Department of Microbiology and Immunology

Steven B. Wells

Columbia University - Department of Systems Biology

Aaron M. Rosenfeld

University of Pennsylvania - Department of Pathology and Laboratory Medicine

Maigan A. Brusko

University of Florida - Department of Pathology, Immunology, and Laboratory Medicine

Todd M. Brusko

University of Florida - Department of Pathology, Immunology, and Laboratory Medicine

Thomas J. Connors

Columbia University - Department of Pediatrics

Alessandro Sette

La Jolla Institute for Immunology - Center for Infectious Disease and Vaccine Research; La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Peter A. Sims

Columbia University - Department of Systems Biology

Eline T. Luning Prak

University of Pennsylvania - Department of Pathology and Laboratory Medicine

Yufeng Shen

Columbia University - Department of Systems Biology

Donna Farber

Columbia University - Department of Microbiology and Immunology; Columbia University - Columbia Center for Translational Immunology; Columbia University, Columbia University Medical Center, Department of Surgery

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Abstract

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

Suggested Citation

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.

Maya M.L. Poon

Columbia University - Department of Microbiology and Immunology

3022 Broadway
New York, NY 10027
United States

Eve Byington

Columbia University - Department of Systems Biology

3022 Broadway
New York, NY 10027
United States

Wenzhao Meng

University of Pennsylvania - Department of Pathology and Laboratory Medicine

Philadelphia, PA 19104
United States

Masaru Kubota

Columbia University - Department of Surgery ( email )

New York, NY
United States

Rei Matsumoto

Columbia University - Department of Surgery

3022 Broadway
New York, NY 10027
United States

Alba Grifoni

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Daniela Weiskopf

La Jolla Institute for Immunology - Center for Infectious Disease and Vaccine Research

United States

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Pranay Dogra

Columbia University - Department of Microbiology and Immunology

3022 Broadway
New York, NY 10027
United States

Nora Lam

Columbia University Irving Medical Center - Department of Pathology and Cell Biology ( email )

New York, NY 10032
United States

Peter A. Szabo

Columbia University - Department of Microbiology and Immunology

3022 Broadway
New York, NY 10027
United States

Basak Burcu Ural

Columbia University - Department of Microbiology and Immunology

3022 Broadway
New York, NY 10027
United States

Steven B. Wells

Columbia University - Department of Systems Biology

3022 Broadway
New York, NY 10027
United States

Aaron M. Rosenfeld

University of Pennsylvania - Department of Pathology and Laboratory Medicine

Philadelphia, PA 19104
United States

Maigan A. Brusko

University of Florida - Department of Pathology, Immunology, and Laboratory Medicine

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Todd M. Brusko

University of Florida - Department of Pathology, Immunology, and Laboratory Medicine

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Thomas J. Connors

Columbia University - Department of Pediatrics

3022 Broadway
New York, NY 10027
United States

Alessandro Sette

La Jolla Institute for Immunology - Center for Infectious Disease and Vaccine Research

United States

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Peter A. Sims

Columbia University - Department of Systems Biology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Eline T. Luning Prak

University of Pennsylvania - Department of Pathology and Laboratory Medicine

Philadelphia, PA 19104
United States

Yufeng Shen

Columbia University - Department of Systems Biology

3022 Broadway
New York, NY 10027
United States

Donna Farber (Contact Author)

Columbia University - Department of Microbiology and Immunology ( email )

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Columbia University - Columbia Center for Translational Immunology ( email )

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Columbia University, Columbia University Medical Center, Department of Surgery ( email )

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

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