IMPAIRED IGG PRODUCTION IN THE LUNGS OF HIV-INFECTED INDIVIDUALS

Human immunodeficiency virus (HIV)-infected individuals are at risk fo r pulmonary infections with encapsulated bacterial pathogens. This cou ld reflect impaired production of opsonizing antibodies in the lower r espiratory tract. We examined antibody production in the alveolar spac e by measuring immunoglobulin concentrations in bronchoalveolar lavage (BAL) of HIV-infected patients and normal volunteers and by assessing the ability of alveolar macrophages (AM) to induce immunoglobulin pro duction in normal peripheral blood mononuclear cells (PBMC). BAL from HIV-infected patients contained significantly less IgG than normal BAL . IgA and IgM concentrations were similar in both groups. Normal AM su pported IgG and IgA production in PBMC. While HIV AM could induce IgA production in PBMC, in no instance did they induce IgG secretion. HIV AM produced significantly more transforming growth factor-beta (TGF-be ta), a factor known to suppress IgG production, than normal AM. Finall y, TGF-beta antibodies blocked the inhibitory effect of HIV AM on norm al IgG secretion without affecting IgA secretion. These findings demon strate impaired production of opsonizing IgG in the alveolar space of HIV-infected subjects and implicate excess TGF-beta production by AM a s the cause of this impairment. (C) 1996 Academic Press, Inc.