Evidence that human CD8+CD45RA+CD27- cells are induced by antigen and evolve through extensive rounds of division

We recently showed that circulating human CD8(+) effector cells have a CD45RA(+)CD27(-) membrane phenotype, In itself this phenotype appeared to pose a paradox: CD45RA, a marker expressed by unprimed cells, combined with absence of CD27, characteristic for chronically stimulated T cells. To investigate whether differentiation towards the CD45RA(+)CD27(-) phenotype is dependent on antigenic stimulation and involves cellular division, TCR V-beta usage and telomeric restriction fragment (TRF) length were analyzed within distinct peripheral blood CD8(+) subsets. FAGS analysis showed that the TCR V-beta repertoire of CD8(+)CD45RA(+)CD27(+) cells differed significantly from that of unprimed CD8(+)CD45RA(+)CD27(+) cells. Moreover, in two out of six individuals large expansions of particular V-beta families were observed in the CD8(+)CD45RA(+)CD27(-) subset. CDR3 spectrotyping and single-strand confirmation analysis revealed that within the CD8(+)CD45RA(+)CD27(-) population most of the 22 tested V-beta families were dominated by oligoclonal expansions, The mean TRF length was found to be 2.3 +/- 1.0 kb shorter in the CD8(+)CD45RA(+)CD27(-) subset compared with the unprimed CD8(+)CD45RA(+)CD27(+) population, but did not differ substantially from that of memory type, CD8(+)CD45RA(-)CD27(+) T cells. These findings indicate that the CD8(+)CD45RA(+)CD27(-) cytotoxic effector population consists of antigen-induced, clonally expanded cells and confirm that the expression of CD45RA is not a strict marker of antigen non-experienced T cells.