Aging leads to disturbed homeostasis of memory phenotype CD8(+) cells.
Examining the rate of in vivo T cell turnover (proliferation) in aged mice revealed a marked reduction in turnover at the level of memory-phenotype CD44(hi) CD8(+) cells relative to young mice. Based on adoptive transfer experiments, the reduced turnover of aged CD44(hi) CD8(+) cells reflected an inhibitory influence of the aged host environment. Aged CD44(hi) CD8(+) cells also showed poor in vivo responses to IL-15 and IL-15-inducing agents, but responded well to IL-15 in vitro. Two mechanisms could account for the reduced turnover of aged CD44(hi) CD8(+) cells in vivo. First, aging was associated with a prominent and selective increase in Bcl-2 expression in CD44(hi) CD8(+) cells. Hence, the reduced turnover of aged CD44(hi) CD8(+) cells may in part reflect the antiproliferative effect of enhanced Bcl-2 expression. Second, the impaired in vivo response of aged CD44(hi) CD8(+) cells to IL-15 correlated with increased serum levels of type I interferons (IFN-I) and was largely reversed by injection of anti-IFN-I antibody. Hence the selective reduction in the turnover of aged CD44(hi) CD8(+) cells in vivo may reflect the combined inhibitory effects of enhanced Bcl-2 expression and high IFN-I levels.
Zhang
Xiaohong
X
Department of Immunology, IMM4 The Scripps Research Institute, La Jolla, CA 92037, USA.
Fujii
Hideki
H
Kishimoto
Hidehiro
H
LeRoy
Eric
E
Surh
Charles D
CD
Sprent
Jonathan
J
D019264:Adoptive Transfer; D000375:Aging / Q000276:immunology*; D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015870:Gene Expression; D019254:Genes, bcl-2; D006706:Homeostasis / Q000276:immunology; D018960:Hyaluronan Receptors / Q000378:metabolism; D007156:Immunologic Memory; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D019409:Interleukin-15 / Q000235:genetics / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D018960:Hyaluronan Receptors; D019409:Interleukin-15; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D016899:Interferon-beta