Effects of 7,12-dimethylbenz[ a]anthracene on the superantigen toxic shock syndrome toxin (TSST-1)-induced proliferation and antibody secretion by human lymphocytes

Abstract

Toxic shock syndrome toxin (TSST-1), a 22-kDa exotoxin secreted by Staphylococcus aureus, can act as a nominal antigen and induce proliferation and immunoglobulin secretion in human B-cells. The purpose of the present studies was to examine the effect of 7,12-dimethylbenz[a]anthracene (DMBA), a well-characterized immunosuppressant of both cell-mediated and humoral immunity in murine lymphocytes, upon the mixed lymphocyte reaction (MLR) and TSST-1-induced immune responses in human lymphocytes. The MLR, using human tonsillar lymphocytes (HTL) from four different donors, was inhibited in a dose-dependent manner from 1 to 100 microM. The IC50 for the suppression of the MLR ranged from 10 to 40 microM. TSST-1 is a potent stimulator of T-cells bearing specific VB regions on the T-cell receptor (TCR). In contrast with the results from the MLR, DMBA inhibited TSST-1-induced T-cell proliferation only at 100 microM in HTL. A similar profile of activity was determined with splenic T-cells from a single donor. TSST-1 has also been demonstrated to induce specific B-cell proliferation and differentiation in the presence of irradiated T-cells. TSST-1-induced B-cell proliferation was only consistently and markedly inhibited by DMBA at 100 microM in tonsillar and splenic lymphocytes. In contrast, TSST-1-induced B-cell differentiation, as manifested by IgM and IgG secretion, was inhibited in a dose-dependent manner from 1 to 100 microM DMBA in B-cells from human tonsils and spleens.(ABSTRACT TRUNCATED AT 250 WORDS)