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Immunization-induced antigen archiving enhances local memory CD8+ T cell responses following an unrelated viral infection.

ABSTRACT: Antigens from viruses or immunizations can persist or are archived in lymph node stromal cells such as lymphatic endothelial cells (LEC) and fibroblastic reticular cells (FRC). Here, we find that, during the time frame of antigen archiving, LEC apoptosis caused by a second, but unrelated, innate immune stimulus such as vaccina viral infection or CpG DNA administration resulted in cross-presentation of archived antigens and boosted memory CD8 + T cells specific to the archived antigen. In contrast to "bystander" activation associated with unrelated infections, the memory CD8 + T cells specific to the archived antigen from the immunization were significantly higher than memory CD8 + T cells of a different antigen specificity. Finally, the boosted memory CD8 + T cells resulted in increased protection against Listeria monocytogenes expressing the antigen from the immunization, but only for the duration that the antigen was archived. These findings outline an important mechanism by which lymph node stromal cell archived antigens, in addition to bystander activation, can augment memory CD8 + T cell responses during repeated inflammatory insults.

SUBMITTER: Doan TA

PROVIDER: S-EPMC10957963 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Immunization-induced antigen archiving enhances local memory CD8+ T cell responses following an unrelated viral infection.

Doan Thu A TA Forward Tadg S TS Schafer Johnathon B JB Lucas Erin D ED Fleming Ira I Uecker-Martin Aspen A Ayala Edgardo E Guthmiller Jenna J JJ Hesselberth Jay R JR Morrison Thomas E TE Tamburini Beth A Jirón BAJ

NPJ vaccines 20240321 1

Antigens from viruses or immunizations can persist or are archived in lymph node stromal cells such as lymphatic endothelial cells (LEC) and fibroblastic reticular cells (FRC). Here, we find that, during the time frame of antigen archiving, LEC apoptosis caused by a second, but unrelated, innate immune stimulus such as vaccina viral infection or CpG DNA administration resulted in cross-presentation of archived antigens and boosted memory CD8 + T cells specific to the archived antigen. In contras ...[more]

PMID: 38514656

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Project description:While the brain is considered an immune-privileged site, the CNS may nevertheless be the focus of immune mediated inflammation in the case of infection and certain autoimmune diseases, e.g., multiple sclerosis. As in other tissues, it has been found that acute T-cell infiltration may be followed by establishment of persistent local T-cell memory. To improve our understanding regarding the regulation of putative tissue resident memory T (Trm) cells in CNS, we devised a new model system for studying the generation of Trm cells in this site. To this purpose, we exploited the fact that the CNS may be a sanctuary for adenoviral infection, and to minimize virus-induced disease, we chose replication-deficient adenoviruses for infection of the CNS. Non-replicating adenoviruses are known to be highly immunogenic, and our studies demonstrate that intracerebral inoculation causes marked local T-cell recruitment, which is followed by persistent infiltration of the CNS parenchyma by antigen specific CD8+ T cells. Phenotypical analysis of CNS infiltrating antigen specific CD8+ T cells was consistent with these cells being Trms. Regarding the long-term stability of the infiltrate, resident CD8+ T cells expressed high levels of the anti-apoptotic molecule Bcl-2 as well as the proliferation marker Ki-67 suggesting that the population is maintained through steady homeostatic proliferation. Functionally, memory CD8+ T cells from CNS matched peripheral memory cells with regard to capacity for ex vivo cytotoxicity and cytokine production. Most importantly, our experiments revealed a key role for local antigen encounter in the establishment of sustained CD8+ T-cell memory in the brain. Inflammation in the absence of cognate antigen only led to limited and transient infiltration by antigen specific CD8+ T cells. Together these results indicate that memory CD8+ T cells residing in the CNS predominantly mirror previous local infections and immune responses to local autoantigens.

Dataset Information

Immunization-induced antigen archiving enhances local memory CD8+ T cell responses following an unrelated viral infection.

Publications

Immunization-induced antigen archiving enhances local memory CD8+ T cell responses following an unrelated viral infection.

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