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PMID: 11828003 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Aging leads to disturbed homeostasis of memory phenotype CD8(+) cells.

The Journal of experimental medicine ·Vol. 195 ·No. 3 ·2002-02-04 ·Pages 283-93

Zhang X, Fujii H, Kishimoto H, LeRoy E, Surh CD, Sprent J

Abstract

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.

MeSH Terms
Adoptive Transfer Aging/immunology Animals Apoptosis CD4-Positive T-Lymphocytes/cytology,immunology CD8-Positive T-Lymphocytes/cytology,immunology Gene Expression Genes, bcl-2 Homeostasis/immunology Hyaluronan Receptors/metabolism Immunologic Memory In Vitro Techniques Interferon-beta/antagonists & inhibitors,biosynthesis,genetics Interleukin-15/genetics,pharmacology Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Phenotype Proto-Oncogene Proteins c-bcl-2/genetics RNA, Messenger/genetics,metabolism bcl-X Protein
Chemicals
Bcl2l1 protein, mouse Hyaluronan Receptors Interleukin-15 Proto-Oncogene Proteins c-bcl-2 RNA, Messenger bcl-X Protein Interferon-beta
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zhang Xiaohong
Department of Immunology, IMM4 The Scripps Research Institute, La Jolla, CA 92037, USA.
Fujii Hideki
Kishimoto Hidehiro
LeRoy Eric
Surh Charles D
Sprent Jonathan
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20011267
Published
2002-02-04
Pages
283-93
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193587
Subset
IM
Grants
NCI NIH HHS · CA38355 · United States
NIAID NIH HHS · AI21487 · United States
NIAID NIH HHS · AI32068 · United States
NIA NIH HHS · P01 AG001743 · United States
NCI NIH HHS · R37 CA038355 · United States
NIAID NIH HHS · R01 AI045809 · United States
NIA NIH HHS · AG01743 · United States
NCI NIH HHS · CA25803 · United States
NIAID NIH HHS · AI41079 · United States
External Links
PubMed source DOI: 10.1084/jem.20011267 PMC Full Text View journal details
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