antigen-specific T cells capable of down- modulating cytotoxic activity

Major expansions of CD8 hiF CD57 F T lymphocytes frequently occur during human immunodeficiency virus (HIV) infection and after transplantation. To investigate mechanisms of such cell expansion, we compared the activation and functional status of CD8 hiF CD57 F and CD57 ‐ peripheral blood lymphocytes (PBL) from normal, bone marrow transplantation (BMT) and HIV F donors. The CD8 hiF CD57 F PBL from BMT and HIV F donors preferentially displayed CD38 and HLA-DR activation markers without correlation between CD8 hiF CD57 F percentages and HIV load, the CD45RA F isoform in all ex vivo conditions but acquired CD45RO after in vitro expansion, CD11b and CD11c in BMT and HIV F donors but decreased expression of CD62-L, VLA-2 and VLA-6. The CD8 hiF CD57 F cells were positive for perforin and granzyme B and spontaneously mediated cytolytic activity in a CD3-redirected assay. In contrast the inhibitor of cytolytic functions (ICF) produced by CD8 hiF CD57 F cells down-modulated the CD3-redirected cytolytic activity but only at low levels of CD3 cross-linking. While CD3-triggering induced a low, if any, short-term proliferation of CD8 F CD57 F cells, this subset could be amplified after long-term stimulation either with mitogens or with HIV antigens, thereby enriched in HIV-specific T cells producing tumor necrosis factor-a. Altogether these data suggest that CD8 hiF CD57 F cells represent a terminal differentiation