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 CD45 RA(+)CD27(-) membrane phenotype, In itself this phenotype appeared to pose a paradox: CD45RA, a marker expressed by unprimed cells, combined with abse nce of CD27, characteristic for chronically stimulated T cells. To investig ate whether differentiation towards the CD45RA(+)CD27(-) phenotype is depen dent on antigenic stimulation and involves cellular division, TCR V-beta us age and telomeric restriction fragment (TRF) length were analyzed within di stinct peripheral blood CD8(+) subsets. FAGS analysis showed that the TCR V -beta repertoire of CD8(+)CD45RA(+)CD27(+) cells differed significantly fro m that of unprimed CD8(+)CD45RA(+)CD27(+) cells. Moreover, in two out of si x 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(-) popul ation most of the 22 tested V-beta families were dominated by oligoclonal e xpansions, The mean TRF length was found to be 2.3 +/- 1.0 kb shorter in th e CD8(+)CD45RA(+)CD27(-) subset compared with the unprimed CD8(+)CD45RA(+)C D27(+) population, but did not differ substantially from that of memory typ e, CD8(+)CD45RA(-)CD27(+) T cells. These findings indicate that the CD8(+)C D45RA(+)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.