CROSS-LINKING OF CD30 INDUCES HIV EXPRESSION IN CHRONICALLY INFECTED T-CELLS

CD30, a member of the tumor necrosis factor (TNF) receptor family, is expressed constitutively on the surface of the human T cell line ACH-2 , which is chronically infected with human immunodeficiency virus type -1 (HIV)-1. We demonstrate that cross-linking CD30 with an anti-CD30-s pecific monoclonal antibody, which mimics the described biological act ivities of the CD30 ligand (CD30L), results in HIV expression. CD30 cr oss-linking does not alter proliferation of ACH-2 cells and the induct ion of HIV expression is not mediated by endogenous TNF alpha/beta. Fu rthermore, cross-linking of CD30 leads to NF-kappa B activation and en hanced HIV transcription. Thus, CD30-CD30L interactions mediate the in duction of HIV expression by a kappa B-dependent pathway that is indep endent of TNF. This mechanism may be important in the activation of HI V expression from latently infected CD4(+) T cells, especially in lymp hoid organs where cell to cell contact is conducive to receptor-ligand Interactions.