International Immunology, Vol. 11, No. 7, 1027-1033,
July 1999
© 1999 Japanese Society for Immunology
Evidence that human CD8+CD45RA+CD27– cells are induced by antigen and evolve through extensive rounds of division
1 Department of Clinical Viro-Immunology and
2 Department of Immunobiology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service (CLB) and Laboratory of Experimental and Clinical Immunology, Academic Medical Centre, 1066 CX Amsterdam, The Netherlands
3 Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam,1066 CX Amsterdam, The Netherlands
Correspondence to: R. A. W. van Lier, Dept. Clinical Viro-Immunology, CLB, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands
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 Vß usage and telomeric restriction fragment (TRF) length were analyzed within distinct peripheral blood CD8+ subsets. FACS analysis showed that the TCR Vß 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 Vß 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 Vß 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.
Keywords: CD8, CD27, CD45RA, single-strand confirmation polymorphism, telomeric restriction fragment
Transmitting editor: K. Okumura
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