tetano
Editor, Senior Moderator
Cell Rep
. 2021 Nov 30;37(9):110071.
doi: 10.1016/j.celrep.2021.110071.
Heterogeneity of human anti-viral immunity shaped by virus, tissue, age, and sex
Maya M L Poon[SUP] 1 [/SUP], Eve Byington[SUP] 2 [/SUP], Wenzhao Meng[SUP] 3 [/SUP], Masaru Kubota[SUP] 4 [/SUP], Rei Matsumoto[SUP] 4 [/SUP], Alba Grifoni[SUP] 5 [/SUP], Daniela Weiskopf[SUP] 5 [/SUP], Pranay Dogra[SUP] 6 [/SUP], Nora Lam[SUP] 7 [/SUP], Peter A Szabo[SUP] 6 [/SUP], Basak Burcu Ural[SUP] 6 [/SUP], Steven B Wells[SUP] 2 [/SUP], Aaron M Rosenfeld[SUP] 3 [/SUP], Maigan A Brusko[SUP] 8 [/SUP], Todd M Brusko[SUP] 8 [/SUP], Thomas J Connors[SUP] 9 [/SUP], Alessandro Sette[SUP] 10 [/SUP], Peter A Sims[SUP] 11 [/SUP], Eline T Luning Prak[SUP] 3 [/SUP], Yufeng Shen[SUP] 12 [/SUP], Donna L Farber[SUP] 13 [/SUP]
Affiliations
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[SUP]+[/SUP] 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.
Keywords: T lymphocytes; anti-viral immunity; cytomegalovirus; human immunology; immunological memory; influenza; lymphoid organs; mucosal immunity; tissue resident memory T cells.
. 2021 Nov 30;37(9):110071.
doi: 10.1016/j.celrep.2021.110071.
Heterogeneity of human anti-viral immunity shaped by virus, tissue, age, and sex
Maya M L Poon[SUP] 1 [/SUP], Eve Byington[SUP] 2 [/SUP], Wenzhao Meng[SUP] 3 [/SUP], Masaru Kubota[SUP] 4 [/SUP], Rei Matsumoto[SUP] 4 [/SUP], Alba Grifoni[SUP] 5 [/SUP], Daniela Weiskopf[SUP] 5 [/SUP], Pranay Dogra[SUP] 6 [/SUP], Nora Lam[SUP] 7 [/SUP], Peter A Szabo[SUP] 6 [/SUP], Basak Burcu Ural[SUP] 6 [/SUP], Steven B Wells[SUP] 2 [/SUP], Aaron M Rosenfeld[SUP] 3 [/SUP], Maigan A Brusko[SUP] 8 [/SUP], Todd M Brusko[SUP] 8 [/SUP], Thomas J Connors[SUP] 9 [/SUP], Alessandro Sette[SUP] 10 [/SUP], Peter A Sims[SUP] 11 [/SUP], Eline T Luning Prak[SUP] 3 [/SUP], Yufeng Shen[SUP] 12 [/SUP], Donna L Farber[SUP] 13 [/SUP]
Affiliations
- PMID: 34852222
- DOI: 10.1016/j.celrep.2021.110071
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[SUP]+[/SUP] 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.
Keywords: T lymphocytes; anti-viral immunity; cytomegalovirus; human immunology; immunological memory; influenza; lymphoid organs; mucosal immunity; tissue resident memory T cells.