We reported previously that PBMC from HIV+ patients spontaneously release increased levels of TGFβ1, contributing to defects in cellular immune responses. This study defines the implications of TGFβ 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 TGFβ secretion by PBMC from HIV-infected donors. Conditioned medium from HIV+ PBMC and purified TGFβ1 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 TGFβ as cells from normal donors. Antibodies to TGFβ1 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 TGFβ from HIV+ PBMC is able to significantly reduce the induction of immunoglobulins and this effect was also abrogated by anti-TGFβ. These studies support the concept that in HIV infection, TGFβ is a potent suppressor, not only of the cellular, but of the humoral immune responses as well.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)