Aging boosts antiviral CD8+T cell memory through improvedengagement of diversified recall response determinants

English version

Autoři: Bennett Davenport ^aff001; Jens Eberlein ^aff001; Tom T. Nguyen ^aff001; Francisco Victorino ^aff001; Kevin Jhun ^aff003; Haedar Abuirqeba ^aff003; Verena van der Heide ^aff003; Peter Heeger ^aff004; Dirk Homann ^aff001
Působiště autorů: Department of Anesthesiology & Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, United States of America ^aff001; Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, Colorado, United States of America ^aff002; Diabetes, Obesity & Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America ^aff003; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America ^aff004
Vyšlo v časopise: Aging boosts antiviral CD8+T cell memory through improvedengagement of diversified recall response determinants. PLoS Pathog 15(11): e32767. doi:10.1371/journal.ppat.1008144
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008144

Souhrn

The determinants of protective CD8⁺ memory T cell (CD8⁺T_M) immunity remain incompletely defined and may in fact constitute an evolving agency as aging CD8⁺T_M progressively acquire enhanced rather than impaired recall capacities. Here, we show that old as compared to young antiviral CD8⁺T_M more effectively harness disparate molecular processes (cytokine signaling, trafficking, effector functions, and co-stimulation/inhibition) that in concert confer greater secondary reactivity. The relative reliance on these pathways is contingent on the nature of the secondary challenge (greater for chronic than acute viral infections) and over time, aging CD8⁺T_M re-establish a dependence on the same accessory signals required for effective priming of naïve CD8⁺T cells in the first place. Thus, our findings reveal a temporal regulation of complementary recall response determinants that is consistent with the recently proposed “rebound model” according to which aging CD8⁺T_M properties are gradually aligned with those of naïve CD8⁺T cells; our identification of a broadly diversified collection of immunomodulatory targets may further provide a foundation for the potential therapeutic “tuning” of CD8⁺T_M immunity.

Klíčová slova:

Aging – Blood – Cytotoxic T cells – Immune response – Memory recall – Spleen – T cells – CD coreceptors

Zdroje

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