TY - JOUR
T1 - Aging of antiviral CD8 + memory T cells fosters increased survival, metabolic adaptations, and lymphoid tissue homing
AU - Davenport, Bennett
AU - Eberlein, Jens
AU - van der Heide, Verena
AU - Jhun, Kevin
AU - Nguyen, Tom T.
AU - Victorino, Francisco
AU - Trotta, Andrew
AU - Chipuk, Jerry
AU - Yi, Zhengzi
AU - Zhang, Weijia
AU - Clambey, Eric T.
AU - Scott, Donald K.
AU - Homann, Dirk
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH) AG026518 and AI093637, Juvenile Diabetes Research Foundation Career Development Award 2-2007-240, and Diabetes Endocrinology Research Center P30-DK057516 (to D.H.), American Heart Association 13SDG14510023 (to E.T.C.), and NIH Training Grants T32 AI07405, T32 AI052066, and T32 DK007792 (to B.D.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
Copyright © 2019 by The American Association of Immunologists, Inc.
PY - 2019/1/15
Y1 - 2019/1/15
N2 - 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 M ) homeostasis. Over time, CD8 + T M 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 M quiescence and fitness but also impart the reacquisition of a partial effector-like metabolic profile; and a gradual redistribution of aging CD8 + T M from blood and nonlymphoid tissues to lymphatic organs results in CD8 + T M 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 M poised for greater recall responses.
AB - 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 M ) homeostasis. Over time, CD8 + T M 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 M quiescence and fitness but also impart the reacquisition of a partial effector-like metabolic profile; and a gradual redistribution of aging CD8 + T M from blood and nonlymphoid tissues to lymphatic organs results in CD8 + T M 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 M poised for greater recall responses.
UR - http://www.scopus.com/inward/record.url?scp=85059928826&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1801277
DO - 10.4049/jimmunol.1801277
M3 - Article
C2 - 30552164
AN - SCOPUS:85059928826
SN - 0022-1767
VL - 202
SP - 460
EP - 475
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -