TRANSFORMING GROWTH-FACTOR-BETA AND SUPPRESSION OF HUMORAL IMMUNE-RESPONSES IN HIV-INFECTION

We reported previously that PBMC from HIV+ patients spontaneously release increased levels of TGF-beta-1, contributing to defects in cellular immune responses. This study defines the implications of TGF-beta overexpression for humoral immunity in HIV infection. We found that upon Staphylococcus aureus Cowan I (SAC) stimulation of cells from HIV+ donors, B-lymphocyte proliferative responses were decreased. This deficiency correlated closely (r = 0.7, P < 0.001) with increased TGF-beta secretion by PBMC from HIV-infected donors. Conditioned medium from HIV+ PBMC and purified TGF-beta-1 had similar inhibitory effects on SAC- or EBV-induced B-cell proliferation, and B cells from HIV-infected donors were as sensitive to inhibition by TGF-beta as cells from normal donors. Antibodies to TGF-beta-1 neutralized the inhibitory effect of HIV+ culture supernatants on normal B cells and increased low proliferative responses by HIV+ cells. Using PWM as stimulus for B cell differentiation, it was shown that activated TGF-beta from HIV+ PBMC is able to significantly reduce the induction of immunoglobulins and this effect was also abrogated by anti-TGF-beta. These studies support the concept that in HIV infection, TGF-beta is a potent suppressor, not only of the cellular, but of the humoral immune responses as well.