EVIDENCE FOR B-CELL-MEDIATED ACTIVATION OF V-DELTA-1(-LYMPHOCYTES DURING PROGRESSION OF HIV-INFECTION() T)

Progression of HIV-induced immunodeficiency is associated with both B cell activation and an increased proportion of V delta 1(+) T cells in PBL, To examine whether the peripheral expansion of V delta 1(+) cell s is driven by activated B cells, we isolated CD19(+) PBL from HIV+ in dividuals at different stages of infection and used them to stimulate V delta 1(+) T cell clones, The V delta 1(+) T cell clones were isolat ed from HIV+ individuals and selected on the basis of cytotoxic activi ty and IFN-gamma expression in response to lymphoblastoid cell lines ( LCLs) established from patients with AIDS (AIDS-related LCLs) but not LCLs of HIV- donors, Peripheral blood B cells from HIV+ patients induc ed IFN-gamma expression in these V delta 1(+) clones, and their stimul atory ability was associated with up-regulated expression of the CD38 activation Ag and with a 6- to 10-fold increased spontaneous Ig produc tion, Stimulation of CD19(+) PBL from HIV+ individuals with cross-link ed anti-CD40 mAb or rgp120 further augmented induction of IFN-gamma ex pression in the V gamma 1(+) cells, The isolated V delta 1(+) T cell c lones expressed the J delta 1 gene segment, but differed in V gamma ge ne segment usage and in the junctional region of TCR-delta chains, ind icating V delta gene-determined recognition, These results provide evi dence that the peripheral expansion of V delta 1(+) cells in HIV infec tion is associated with phenotypic and functional alterations of B cel ls, due to chronic activation during progression to AIDS.