CD8hi+CD57+ T lymphocytes are enriched in antigen-specific T cells capable of down-modulating cytotoxic activity

Major expansions of CD8(hi+)CD57(+) 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(hi+)CD57(+) and CD57(-) peripheral blood lymphocytes (PBL) from normal, bone marrow transplantation (BMT) and HIV+ donors, The CD8(hi+)CD57(+) PBL from BMT and HIV+ donors preferentially displayed CD38 and HLA-DR activation markers without correlation between CD8(hi+)CD57(+) percentages and HIV load, the CD45RA(+) isoform in all ex vivo conditions but acquired CD45RO after in vitro expansion, CD11b and CD11c in BMT and HIV+ donors but decreased expression of CD62-L, VLA-2 and VLA-6, The CD8(hi+)CD57(+) 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(hi+)CD57(+) 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(+)CD57(+) 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-alpha, Altogether these data suggest that CD8(hi+)CD57(+) cells represent a terminal differentiation state of activated effector cytotoxic T lymphocytes which are enriched in antigen-specific T cells and down-modulate their own cytolytic potential, thus participating in a negative control of effector cell functions during persistent viral infections or transplantations.