CD8hi+CD57+ T lymphocytes are enriched in antigen-specific T cells capable of down-modulating cytotoxic activity |
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Authors: | Mollet L; Sadat-Sowti B; Duntze J; Leblond V; Bergeron F; Calvez V; Katlama C; Debre P; Autran B |
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Institution: | Laboratoire d'Immunologie Cellulaire et Tissulaire, CNRS-URA 625, CHU Pitie-Salpetriere, Paris, France. |
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Abstract: | Major expansions of CD8hi+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 CD8hi+CD57+ and CD57-peripheral blood lymphocytes
(PBL) from normal, bone marrow transplantation (BMT) and HIV+ donors. The
CD8hi+CD57+ PBL from BMT and HIV+ donors preferentially displayed CD38 and
HLA-DR activation markers without correlation between CD8hi+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 CD8hi+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 CD8hi+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 CD8hi+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.
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