Role for macrophages and thymus-derived lymphocytes in cholera toxin-induced immunosuppression

The exo-enterotoxin derived from Vibrio cholerae bacilli has marked immunomodulating activities, both in vivo and in vitro. In the present study, the mechanism whereby cholera toxin depresses the antibody-forming ability of murine splenocytes was investigated by in vitro reconstitution experiments. Spleen cells derived from mice treated with cholera toxin 2 days earlier were markedly deficient in their ability to respond to sheep erythrocytes upon challenge immunization in vitro. Addition of graded numbers of normal spleen cells to spleen cell cultures from toxin-treated mice partially restored the antibody response. Adherent splenocyte populations were even more effective in restoring antibody formation. Normal peritoneal exudate cells rich in macrophages were also capable of restoring the antibody-forming ability of toxin-pretreated splenocytes. Furthermore, thymus (T)-derived spleen cells from normal mice, as well as sheep erythrocyte "educated" T cells, were capable of restoring antibody formation to normal levels. The importance of T lymphocytes in restoring immune competence of spleen cell cultures from toxin-treated mice was shown by additional experiments in which T-depleted cell preparations were found to be ineffective in restoring antibody activity. These studies point to macrophages and T-derived lymphocytes as a major target for cholera toxin-induced immunosuppression.