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

• Published in: International immunology Vol. 11; no. 7; pp. 1027 - 1033
• Main Authors: Hamann, Dörte, Kostense, Stefan, Wolthers, Katja C., Otto, Sigrid A., Baars, Paul A., Miedema, Frank, van Lier, René A. W.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.07.1999; Oxford Publishing Limited (England)
• Subjects: CD27; CD45RA; CD8; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - immunology; Cell Division - immunology; Epitopes, T-Lymphocyte - immunology; Humans; Immunologic Memory; Immunophenotyping; Leukocyte Common Antigens - biosynthesis; Leukocyte Common Antigens - immunology; Leukocyte Common Antigens - metabolism; PBMC peripheral blood mononuclear cell; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Antigen, T-Cell, alpha-beta - metabolism; single-strand confirmation polymorphism; SSCP single-strand confirmation polymorphism; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Telomere - immunology; telomeric restriction fragment; TRF telomeric restriction fragment; Tumor Necrosis Factor Receptor Superfamily, Member 7 - biosynthesis; Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/11.7.1027

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