AEGiS-15IAC: CD25+CD4+ regulatory T (Treg)-like cells generated in vitro from naïve human T cells suppress HIV replication in in vitro infected primary CD4+ T cells.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

CD25+CD4+ regulatory T (Treg)-like cells generated in vitro from naïve human T cells suppress HIV replication in in vitro infected primary CD4+ T cells.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrA1006)

Kinter AL, Kern S, Hennessey M, Lin Y, Jackson R, Fauci AS
Lab of Immunoregulation/NIAID/NIH, Bethesda, United States

BACKGROUND: Human CD25+CD4+ Treg-like cells generated in vitro from CD25- CD4+ T cells have been demonstrated to possess phenotypic and functional characteristics similar or identical to freshly isolated immunosuppressive CD25+CD4+ Treg cells. It is believed that generation of Treg-like cells can occur under certain T cell priming conditions in vivo and that these cells can suppress antigen-specific responses; however, the direct effect of this cellular population on HIV replication has not previously been described.

METHODS: Naive CD4+ T cells were activated with allogeneic monocytes in the presence of transforming growth factor (TGF)-b and CD25+ or CD25- subsets were subsequently isolated by immunomagnetic beads. In parallel, total autologous CD4+ T cells, pre-activated with IL-2 plus PHA or allo Ag, were exposed to X4 or R5 HIV strains, washed and then co-cultured with either total or CD25+ and CD25- subsets of TGF-b activated CD4+ T cells (T r/s). HIV replication was assessed by either supernatant or intracellular p24 detection methods. In addition, cellular proliferation (thymidine uptake or CFSE), expression of surface activation markers (FACS) and cytokine neutralization assays were performed.

RESULTS: Total or CD25+, but not CD25-, T r/s cells significantly (up to 95%; p<0.05) suppressed the replication of R5, and to a lesser extent X4, HIV. Inhibition of HIV replication was dependent on the ratio of Tr/s cells in culture and was not associated with significant decreases in CD4+ target T cell proliferation or expression of cell surface activation markers. HIV replication was partially rescued by treatment with neutralizing antibodies directed at CCR5 ligands, TGF-b and IL-10.

CONCLUSIONS: CD4+ T cells with Treg-like activity, generated under certain T cell priming conditions, suppress HIV replication in vitro and may do so in vivo.

Keywords: AEGIS, Receptors, Interleukin-2, Antigens, CD4, T-Lymphocytes, Cell Proliferation, Lymphocyte Activation, CD4-Positive T-Lymphocytes, Interleukin-2, Interleukin-10, Humans, Animal, In Vitro, immunology

040711
MoOrA1006