期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 5, 页码 1333-1338出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1525167113
关键词
naive CD8(+) T cells; aging; CD44(+) virtual memory; influenza A virus; CD5
资金
- National Health and Medical Research Council (NHMRC) [AI1071916, AI1046333]
- National Institutes of Health [U19AI117891, AI107625]
- Sylvia and Charles Viertel Senior Medical Research Fellowship
- Australian Research Council Future Fellowship
- NHMRC Biomedical Postgraduate Scholarship [AI520643]
- NHMRC Centre of Research Excellence Grant [AI1035261]
In advanced age, decreased CD8(+) cytotoxic T-lymphocyte (CTL) responses to novel pathogens and cancer is paralleled by a decline in the number and function of naive CTL precursors (CTLp). Although the age-related fall in CD8(+) T-cell numbers is well established, neither the underlying mechanisms nor the extent of variation for different epitope specificities have been defined. Furthermore, naive CD8(+) T cells expressing high levels of CD44 accumulate with age, but it is unknown whether this accumulation reflects their preferential survival or an age-dependent driver of CD8(+) T-cell proliferation. Here, we track the number and phenotype of four influenza A virus (IAV)-specific CTLp populations in naive C57BL/6 (B6) mice during aging, and compare T-cell receptor (TCR) clonal diversity for the CD44hi and CD44lo subsets of one such population. We show differential onset of decline for several IAV-specific CD8(+) T-cell populations with advanced age that parallel age-associated changes in the B6 immunodominance hierarchy, suggestive of distinct impacts of aging on different epitope-specific populations. Despite finding no evidence of clonal expansions in an aged, epitope-specific TCR repertoire, non-random alterations in TCR usage were observed, along with elevated CD5 and CD8 coreceptor expression. Collectively, these data demonstrate that naive CD8(+) T cells expressing markers of heightened self-recognition are selectively retained, but not clonally expanded, during aging.
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