Age-related modifications of the human alphabeta T cell repertoire due to different clonal expansions in the CD4+ and CD8+ subsets.
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.
Wack
A
A
Unità d'Immunochimica, DIBIT, Istituto Scientifico H. San Raffaele, Milano, Italy.
Cossarizza
A
A
Heltai
S
S
Barbieri
D
D
D'Addato
S
S
Fransceschi
C
C
Dellabona
P
P
Casorati
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000276:immunology*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002999:Clone Cells; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000097:blood / Q000276:immunology*; D016176:T-Lymphocyte Subsets
D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens