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

Major expansions of CD8hiFCD57F 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 CD8hiFCD57F and CD57– peripheral blood lymphocytes (PBL) from normal, bone marrow transplantation (BMT) and HIVF donors. The CD8hiFCD57F PBL from BMT and HIVF donors preferentially displayed CD38 and HLA-DR activation markers without correlation between CD8hiFCD57F percentages and HIV load, the CD45RAF isoform in all ex vivo conditions but acquired CD45RO after in vitro expansion, CD11b and CD11c in BMT and HIVF donors but decreased expression of CD62-L, VLA-2 and VLA-6. The CD8hiFCD57F 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 CD8hiFCD57F 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 CD8FCD57F 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-α. Altogether these data suggest that CD8hiFCD57F 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.