Semi-allogeneic cell hybrids stimulate HIV-1 envelope-specific cytotoxic Tlymphocytes

Objective: The present study was designed to determine whether the HLA allo geneic T helper response stimulated by semi-allogeneic cell lines could be used as an in vitro model of immune-based therapy to stimulate HIV-specific cytotoxic T lymphocytes. Design and methods: Semi-allogeneic cell hybrids were obtained by the fusio n of peripheral blood mononuclear cells from HIV-infected patients with the allogeneic beta 2-microglobulin-deficient FO1-12 melanoma cell line. These hybrids were used as antigen presenting cells for HIV envelope peptide (en v)-specific cytotoxic assays. Results: The hybrid cell lines express HLA class I and II antigens from bot h parental cells, as well as the CD86 costimulatory molecule. HIV-specific cytotoxic T lymphocyte activity was obtained when patients' peripheral bloo d mononuclear cells were costimulated with env peptides plus semi-allogenei c hybrids, in contrast with stimulation with either env or hybrid cells alo ne. Thus, the semi-allogeneic hybrids enhanced HIV-specific killing of targ et cells. Conclusions: Irradiated, semi-allogeneic cell hybrids engineered for indivi dual AIDS patients provide efficient and simultaneous co-recognition of HLA allogeneic determinants and viral antigenic determinants presented by self -HLA molecules on the same antigen presenting cells and results in the gene ration of enhanced HIV-specific cytotoxic T lymphocyte activity. (C) 2000 L ippincott Williams & Wilkins.