Age-related modifications of the human alphabeta T cell repertoire due to different clonal expansions in the CD4+ and CD8+ subsets |
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Authors: | Wack A; Cossarizza A; Heltai S; Barbieri D; D'Addato S; Fransceschi C; Dellabona P; Casorati G |
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Institution: | Unita d'Immunochimica, DIBIT, Istituto Scientifico H. San Raffaele, Milano, Italy. |
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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.
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