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Aging of Antiviral CD8 Memory T Cells Fosters Increased Survival, Metabolic Adaptations, and Lymphoid Tissue Homing.

Citation
Davenport, B., et al. “Aging Of Antiviral Cd8 Memory T Cells Fosters Increased Survival, Metabolic Adaptations, And Lymphoid Tissue Homing.”. Journal Of Immunology (Baltimore, Md. : 1950), pp. 460-475.
Center University of Colorado Denver
Author Bennett Davenport, Jens Eberlein, Verena van der Heide, Kevin Jhun, Tom T Nguyen, Francisco Victorino, Andrew Trotta, Jerry Chipuk, Zhengzi Yi, Weijia Zhang, Eric T Clambey, Donald K Scott, Dirk Homann
Abstract

Aging of established antiviral T cell memory can foster a series of progressive adaptations that paradoxically improve rather than compromise protective CD8 T cell immunity. We now provide evidence that this gradual evolution, the pace of which is contingent on the precise context of the primary response, also impinges on the molecular mechanisms that regulate CD8 memory T cell (T) homeostasis. Over time, CD8 T generated in the wake of an acute infection with the natural murine pathogen lymphocytic choriomeningitis virus become more resistant to apoptosis and acquire enhanced cytokine responsiveness without adjusting their homeostatic proliferation rates; concurrent metabolic adaptations promote increased CD8 T quiescence and fitness but also impart the reacquisition of a partial effector-like metabolic profile; and a gradual redistribution of aging CD8 T from blood and nonlymphoid tissues to lymphatic organs results in CD8 T accumulations in bone marrow, splenic white pulp, and, particularly, lymph nodes. Altogether, these data demonstrate how temporal alterations of fundamental homeostatic determinants converge to render aged CD8 T poised for greater recall responses.

Year of Publication
2019
Journal
Journal of immunology (Baltimore, Md. : 1950)
Volume
202
Issue
2
Number of Pages
460-475
Date Published
12/2019
ISSN Number
1550-6606
DOI
10.4049/jimmunol.1801277
Alternate Journal
J. Immunol.
PMID
30552164
PMCID
PMC6358025
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