期刊
JOURNAL OF IMMUNOLOGY
卷 176, 期 1, 页码 301-308出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.176.1.301
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资金
- NCRR NIH HHS [RR0163] Funding Source: Medline
- NIAID NIH HHS [5T32 AI007472-10] Funding Source: Medline
- NIA NIH HHS [R01 AG020719, AG20719] Funding Source: Medline
- NATIONAL CENTER FOR RESEARCH RESOURCES [P51RR000163] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [T32AI007472] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R37AG020719, R01AG020719] Funding Source: NIH RePORTER
T cell aging manifests itself both at the cellular (cell-autonomous defects in signaling) and at the population (age-related dysregulation of T cell homeostasis) levels. A prominent contributor to the latter is the appearance of T cell clonal expansions (TCE), with a potential to impair immune defense. In this study, we investigated molecular, cellular, and Ag requirements for TCE development. Of the mutant mice tested, old animals lacking MHC class I exhibited 7-fold fewer TCE than controls, with a 7-fold reduction in TCE. By contrast, animals lacking only one of the MHC class I molecules (K-b or D-b), or IL-7R, or devoid of T cell renewal via adult thymectomy, all exhibited significant increases in TCE incidence. This increase directly correlated to lymphopenia, increased CD8 T cell turnover and an accumulation of memory-phenotype T cells. These data suggested that homeostatic cell division in the CD8 compartment enhances the formation of TCE. Repeated immunization with peptide/adjuvant did not result in an increase in Ag-specific TCE; however, adjuvant alone increased TCE incidence. In these experiments, therefore, nonspecific and/or homeostatic proliferation was more efficient in generating TCE in mice than repeated Ag-driven stimulation, suggesting that many, if not most, TCE in specific pathogen-free laboratory mice maybe Ag-independent.
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