Age-related modifications of the human alphabeta T cell repertoire due to different clonal expansions in the CD4+ and CD8+ subsets.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Age-related modifications of the human alphabeta T cell repertoire due to different clonal expansions in the CD4+ and CD8+ subsets.

Int Immunol. 1998 Sep;10(9):1281-8. Unique Identifier : AIDSLINE MED/99000393
Wack A; Cossarizza A; Heltai S; Barbieri D; D'Addato S; Fransceschi C; Dellabona P; Casorati G; Unita d'Immunochimica, DIBIT, Istituto Scientifico H. San; Raffaele, Milano, Italy.

Abstract: We have studied the effects of a life-long antigen stimulation on the clonal heterogeneity of human peripheral T cell subsets, as defined by their CD45 isoform expression. CD4+ or CD8+ T cells were obtained from healthy donors ranging in age from 20 to 100 years, and sorted into CD45RA+ and CD45RO+ populations. A modified PCR-heteroduplex analysis was then used to directly compare the TCR Vbeta clonal make up of either compartment pair. We find that the CD4+ T cell repertoire remains largely polyclonal throughout life, since CD4+ expanded clones are rare and accumulate predominantly in the CD45RO+ compartment of exceptionally old donors (100 years old). In contrast, the CD8+ T cell subset contains expanded clones which are already detectable in young adults and become very frequent in 70- to 75-year-old donors in both CD45RA+ and CD45RO+ compartments analyzed. Interestingly, some expanded clones are detectable in the CD45RA+ or in both CD45RA+ and CD45RO+ compartments of either CD4+ or CD8+ T cells. These results indicate that the age-dependent accumulation of expanded clones starts earlier and is more pronounced in the CD8+ than in the CD4+ T cell subset, reinforcing the concept that clonal expansion in the two subsets is controlled by substantially different mechanisms. Furthermore, whereas the finding of expanded CD45RO+ T cell clones is explained by antigen-driven proliferation, the detection of expanded clones in the CD45RA+ or in both CD45RA+ and CD45RO+ compartments would support the hypothesis of reversion from the CD45RO+ to the CD45RA+ phenotype after antigen encounter.

Keywords: JOURNAL ARTICLE Adult Aged Aged, 80 and over Aging/BLOOD/*IMMUNOLOGY Antigens, CD45/BLOOD/IMMUNOLOGY Clone Cells *CD4-CD8 Ratio CD4-Positive T-Lymphocytes/CYTOLOGY/IMMUNOLOGY CD8-Positive T-Lymphocytes/CYTOLOGY/IMMUNOLOGY Female Human Male Middle Age Polymerase Chain Reaction Receptors, Antigen, T-Cell, alpha-beta/BLOOD/*IMMUNOLOGY Support, Non-U.S. Gov't *T-Lymphocyte Subsets
990330
A9931116

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