CD8(HI-LYMPHOCYTES ARE ENRICHED IN ANTIGEN-SPECIFIC T-CELLS CAPABLE OF DOWN-MODULATING CYTOTOXIC ACTIVITY()CD57(+) T)

Major expansions of CD8(hi+)CD57(+) T lymphocytes frequently occur dur ing human immunodeficiency virus (HIV) infection and after transplanta tion. To investigate mechanisms of such cell expansion, we compared th e activation and functional status of CD8(hi+)CD57(+) and CD57(-) peri pheral blood lymphocytes (PBL) from normal, bone marrow transplantatio n (BMT) and HIV+ donors, The CD8(hi+)CD57(+) PBL from BMT and HIV+ don ors preferentially displayed CD38 and HLA-DR activation markers withou t correlation between CD8(hi+)CD57(+) percentages and HIV load, the CD 45RA(+) 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 cytol ytic activity in a CD3-redirected assay, In contrast the inhibitor of cytolytic functions (ICF) produced by CD8(hi+)CD57(+) cells down-modul ated the CD3-redirected cytolytic activity but only at low levels of C D3 cross-linking, While CD3-triggering induced a low, if any, short-te rm proliferation of CD8(+)CD57(+) cells, this subset could be amplifie d after long-term stimulation either with mitogens or with HIV antigen s, thereby enriched in HIV-specific T cells producing tumor necrosis f actor-alpha, Altogether these data suggest that CD8(hi+)CD57(+) cells represent a terminal differentiation state of activated effector cytot oxic T lymphocytes which are enriched in antigen-specific T cells and down-modulate their own cytolytic potential, thus participating in a n egative control of effector cell functions during persistent viral inf ections or transplantations.