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

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Dec 1

PMID 34852222

Citations 30

Authors

Maya M L Poon

Eve Byington

Wenzhao Meng

Masaru Kubota

Rei Matsumoto

Alba Grifoni

Daniela Weiskopf

Pranay Dogra

Nora Lam

Peter A Szabo

Basak Burcu Ural

Steven B Wells

Aaron M Rosenfeld

Maigan A Brusko

Todd M Brusko

Thomas J Connors

Alessandro Sette

Peter A Sims

Eline T Luning Prak

Yufeng Shen

Donna L Farber

Affiliations

Soon will be listed here.

Abstract

The persistence of anti-viral immunity is essential for protection and exhibits profound heterogeneity across individuals. Here, we elucidate the factors that shape maintenance and function of anti-viral T cell immunity in the body by comprehensive profiling of virus-specific T cells across blood, lymphoid organs, and mucosal tissues of organ donors. We use flow cytometry, T cell receptor sequencing, single-cell transcriptomics, and cytokine analysis to profile virus-specific CD8 T cells recognizing the ubiquitous pathogens influenza and cytomegalovirus. Our results reveal that virus specificity determines 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 are highly correlated with the site. Together, our results demonstrate how the covariates of virus, tissue, age, and sex impact the anti-viral immune response, which is important for targeting, monitoring, and predicting immune responses to existing and emerging viruses.

Citing Articles

Deep profiling deconstructs features associated with memory CD8 T cell tissue residence.

Scott M, Steier Z, Pierson M, Stolley J, OFlanagan S, Soerens A Immunity. 2024; 58(1):162-181.e10.

PMID: 39708817 PMC: 11852946. DOI: 10.1016/j.immuni.2024.11.007.

Maintenance and functional regulation of immune memory to COVID-19 vaccines in tissues.

Davis-Porada J, George A, Lam N, Caron D, Gray J, Huang J Immunity. 2024; 57(12):2895-2913.e8.

PMID: 39510068 PMC: 11634668. DOI: 10.1016/j.immuni.2024.10.003.

Artificial antigen-presenting cell system reveals CD28's role in modulating T cell functions during human immunodeficiency virus infection.

Kabakibo T, Arnold E, Padhan K, Lemieux A, Ortega-Delgado G, Routy J iScience. 2024; 27(10):110947.

PMID: 39381752 PMC: 11460474. DOI: 10.1016/j.isci.2024.110947.

IRF5 mediates adaptive immunity via altered glutamine metabolism, mTORC1 signaling and post-transcriptional regulation following T cell receptor activation.

Brune Z, Lu A, Moss M, Brune L, Huang A, Matta B bioRxiv. 2024; .

PMID: 39253451 PMC: 11382993. DOI: 10.1101/2024.08.26.609422.

Tissue determinants of the human T cell receptor repertoire.

Sureshchandra S, Henderson J, Levendosky E, Bhattacharyya S, Kastenschmidt J, Sorn A bioRxiv. 2024; .

PMID: 39229002 PMC: 11370363. DOI: 10.1101/2024.08.17.608295.

References

Nazarov V, Pogorelyy M, Komech E, Zvyagin I, Bolotin D, Shugay M . tcR: an R package for T cell receptor repertoire advanced data analysis. BMC Bioinformatics. 2015; 16:175. PMC: 4445501. DOI: 10.1186/s12859-015-0613-1. View

Weiskopf D, Schmitz K, Raadsen M, Grifoni A, Okba N, Endeman H . Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome. Sci Immunol. 2020; 5(48). PMC: 7319493. DOI: 10.1126/sciimmunol.abd2071. View

Frizzell H, Fonseca R, Christo S, Evrard M, Cruz-Gomez S, Zanluqui N . Organ-specific isoform selection of fatty acid-binding proteins in tissue-resident lymphocytes. Sci Immunol. 2020; 5(46). DOI: 10.1126/sciimmunol.aay9283. View

Mackay L, Kallies A . Transcriptional Regulation of Tissue-Resident Lymphocytes. Trends Immunol. 2016; 38(2):94-103. DOI: 10.1016/j.it.2016.11.004. View

Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck 3rd W . Comprehensive Integration of Single-Cell Data. Cell. 2019; 177(7):1888-1902.e21. PMC: 6687398. DOI: 10.1016/j.cell.2019.05.031. View

Bush E, Ray F, Alvarez M, Realubit R, Li H, Karan C . PLATE-Seq for genome-wide regulatory network analysis of high-throughput screens. Nat Commun. 2017; 8(1):105. PMC: 5524642. DOI: 10.1038/s41467-017-00136-z. View

Wu Z, McGoogan J . Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323(13):1239-1242. DOI: 10.1001/jama.2020.2648. View

Pan Y, Tian T, Park C, Lofftus S, Mei S, Liu X . Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. Nature. 2017; 543(7644):252-256. PMC: 5509051. DOI: 10.1038/nature21379. View

Masopust D, Vezys V, Marzo A, Lefrancois L . Preferential localization of effector memory cells in nonlymphoid tissue. Science. 2001; 291(5512):2413-7. DOI: 10.1126/science.1058867. View

10.

Hammarlund E, Lewis M, Hansen S, Strelow L, Nelson J, Sexton G . Duration of antiviral immunity after smallpox vaccination. Nat Med. 2003; 9(9):1131-7. DOI: 10.1038/nm917. View

11.

Wu T, Hu Y, Lee Y, Bouchard K, Benechet A, Khanna K . Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection. J Leukoc Biol. 2013; 95(2):215-24. PMC: 3896663. DOI: 10.1189/jlb.0313180. View

12.

Teijaro J, Turner D, Pham Q, Wherry E, Lefrancois L, Farber D . Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J Immunol. 2011; 187(11):5510-4. PMC: 3221837. DOI: 10.4049/jimmunol.1102243. View

13.

Weisberg S, Carpenter D, Chait M, Dogra P, Gartrell-Corrado R, Chen A . Tissue-Resident Memory T Cells Mediate Immune Homeostasis in the Human Pancreas through the PD-1/PD-L1 Pathway. Cell Rep. 2019; 29(12):3916-3932.e5. PMC: 6939378. DOI: 10.1016/j.celrep.2019.11.056. View

14.

Assarsson E, Bui H, Sidney J, Zhang Q, Glenn J, Oseroff C . Immunomic analysis of the repertoire of T-cell specificities for influenza A virus in humans. J Virol. 2008; 82(24):12241-51. PMC: 2593359. DOI: 10.1128/JVI.01563-08. View

15.

Rosenfeld A, Meng W, Luning Prak E, Hershberg U . ImmuneDB, a Novel Tool for the Analysis, Storage, and Dissemination of Immune Repertoire Sequencing Data. Front Immunol. 2018; 9:2107. PMC: 6161679. DOI: 10.3389/fimmu.2018.02107. View

16.

Kumar B, Ma W, Miron M, Granot T, Guyer R, Carpenter D . Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites. Cell Rep. 2017; 20(12):2921-2934. PMC: 5646692. DOI: 10.1016/j.celrep.2017.08.078. View

17.

Dogra P, Rancan C, Ma W, Toth M, Senda T, Carpenter D . Tissue Determinants of Human NK Cell Development, Function, and Residence. Cell. 2020; 180(4):749-763.e13. PMC: 7194029. DOI: 10.1016/j.cell.2020.01.022. View

18.

Weisberg S, Ural B, Farber D . Tissue-specific immunity for a changing world. Cell. 2021; 184(6):1517-1529. PMC: 7988978. DOI: 10.1016/j.cell.2021.01.042. View

19.

Turner D, Bickham K, Thome J, Kim C, DOvidio F, Wherry E . Lung niches for the generation and maintenance of tissue-resident memory T cells. Mucosal Immunol. 2013; 7(3):501-10. PMC: 3965651. DOI: 10.1038/mi.2013.67. View

20.

Connors T, Scott Baird J, Yopes M, Zens K, Pethe K, M Ravindranath T . Developmental Regulation of Effector and Resident Memory T Cell Generation during Pediatric Viral Respiratory Tract Infection. J Immunol. 2018; 201(2):432-439. PMC: 6039242. DOI: 10.4049/jimmunol.1800396. View