MEMBRANE TUMOR-NECROSIS-FACTOR-ALPHA IS INVOLVED IN THE POLYCLONAL B-CELL ACTIVATION-INDUCED BY HIV-INFECTED HUMAN T-CELLS

INFECTION of CD4+ T cells by human immune deficiency virus-1 (HIV-1) causes severe dysfunction of cellular immunity1-3, but paradoxically results in intense polyclonal activation of B cells, possibly accounting for both hypergammaglobulinaemia and frequent development of B-cell malignancies seen in HIV-infected patients4-7. We have reported that human CD4+ T-cell clones infected with HIV in vitro markedly stimulate immunoglobulin synthesis by B cells through a non-cognate, contact-dependent mechanism8. We show here that HIV-infected T-cell clones do not express the CD40 ligand (CD40L), a molecule critical for non-cognate B-cell activation9, but a small proportion of them do express membrane tumour-necrosis factor (TNF)-alpha. The ability of HIV-infected T-cell clones to induce polyclonal B-cell activation appears to be restricted to TNF-alpha-positive T blasts and is inhibited by antibodies against both TNF-alpha and TNF-alpha receptor. Freshly isolated CD4+ T cells from HIV-infected individuals express TNF-alpha on the cell membrane and induce TNF-alpha-mediated immunoglobulin production by B cells. Thus, membrane TNF-alpha seems to be involved in the polyclonal B-cell activation induced by HIV-infected T cells.