Evidence for B cell-mediated activation of V delta 1 super(+) T lymphocytes during progression of HIV infection

Progression of HIV-induced immunodeficiency is associated with both B cell activation and an increased proportion of V delta 1 super(+) T cells in PBL. To examine whether the peripheral expansion of V delta 1 super(+) cells is driven by activated B cells, we isolated CD19 super(+) PBL from HIV super(+) individuals at different stages of infection and used them to stimulate V delta 1 super(+) T cell clones. The V delta 1 super(+) T cell clones were isolated from HIV super(+) individuals and selected on the basis of cytotoxic activity and IFN- gamma expression in response to lymphoblastoid cell lines (LCLs) established from patients with AIDS (AIDS-related LCLs) but not LCLs of HIV super(-) donors. Peripheral blood B cells from HIV super(+) patients induced IFN- gamma expression in these V delta 1 super(+) clones, and their stimulatory ability was associated with up-regulated expression of the CD38 activation Ag and with a 6- to 10-fold increased spontaneous Ig production. Stimulation of CD19 super(+) PBL from HIV super(+) individuals with cross-linked anti-CD40 mAb or rgp120 further augmented induction of IFN- gamma expression in the V delta 1 super(+) cells. The isolated V delta 1 super(+) T cell clones expressed the J delta 1 gene segment, but differed in V gamma gene segment usage and in the junctional region of TCR- delta chains, indicating V delta gene-determined recognition. These results provide evidence that the peripheral expansion of V delta 1 super(+) cells in HIV infection is associated with phenotypic and functional alterations of B cells, due to chronic activation during progression to AIDS.