Membrane tumour 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 immunity, 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 patients. 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 mechanism. We show here that HIV-infected T-cell clones do not express the CD40 ligand (CD40L), a molecule critical for non-cognate B-cell activation, 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.
Macchia
D
D
Division of Clinical Immunology and Allergology, University of Florence, Italy.
Almerigogna
F
F
Parronchi
P
P
Ravina
A
A
Maggi
E
E
Romagnani
S
S
D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D019013:CD40 Antigens; D023201:CD40 Ligand; D002478:Cells, Cultured; D006041:Goats; D006678:HIV; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006679:HIV Seropositivity / Q000276:immunology; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand