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

Abstract

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(β) usage and telomeric restriction fragment (TRF) length were analyzed within distinct peripheral blood CD8+ subsets. FACS analysis showed that the TCR V(β) 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(β) 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(β) 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.