Postthymic development of CD28-CD8+ T cell subset: age-associated expansion and shift from memory to naive phenotype.
During human aging, one of the major changes in the T cell repertoire is a dramatic expansion of T cells with the atypical CD28-CD8+ phenotype. In this study, we show that this increase is a consequence not only of an expansion in the CD28-CD8+ population but also of a decrease in the number of CD28+CD8+ T cells. The decrease in circulating CD28+CD8+ T cells is dramatically accelerated after the age of 50 and is not accompanied by an equivalent reduction in the CD28+CD8+ subset. Our findings confirm that aging leads to an accumulation of CD45RO+ T cells within the CD28+CD8+ subset as previously observed. Surprisingly, we found an increase in CD45RA+ expression with age in the CD28-CD8+ subset. Immune-phenotyping for activation markers, measurement of telomere DNA content, and cytokine production analysis indicate that the large majority of CD28-CD8+ T cells are Ag-experienced, despite their CD45RA+ phenotype. Our study further demonstrates that the poor proliferative response displayed by CD28-CD8+ T cells is not a consequence of telomere shortening. Also, analysis of cytokine production at the single cell level revealed that the proportions of IFN-gamma +, IL-4+, and IL-10+ T cells are considerably higher among the CD28-CD8+ than the CD28+CD8+ subset. In summary, these data explain the presence of CD45RA+ T cells in the elderly, shed light on the phylogenetic origin of CD28-CD8+ T cells, and suggest a role for these cells in the immune senescence process.
Nociari
M M
MM
Laboratory of Immunology, Cornell University Medical College, New York 10021, USA.
Telford
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W
Russo
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D018106:CD28 Antigens / Q000096:biosynthesis*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology; D016827:CD8 Antigens / Q000096:biosynthesis* / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D004247:DNA / Q000032:analysis; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007399:Interphase / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D016615:Telomere / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000502:physiology
D018106:CD28 Antigens; D016827:CD8 Antigens; D004247:DNA; D017493:Leukocyte Common Antigens