The parameters of Cyclosporine A induced inhibition of a T cell dependent antibody response

Cyclosporine A (CsA) is a widely used immunosuppressive drug which has novel, clinically beneficial effects on the immune system. Substantial evidence indicates that CsA acts preferentially by impairing T cell lymphokine production, but there is some evidence that CsA may also affect B cells and other antigen presenting cells directly. Using an in vitro antibody response to sheep red blood cells, we have examined the effect CsA has on different populations of mouse lymphocytes. CsA appears to have a direct inhibitory effect on highly purified B cells from naive animals in a dose dependent manner at physiologically achievable levels in vitro. Even antigen stimulated B cells were found to be sensitive to the late addition of CsA when the drug was added simultaneously with lymphokine. B cells and T cells briefly pulsed with CsA do not recover to produce antibody when CsA is removed. Indeed, B cells from naive animals treated in vivo with CsA and stimulated in vitro with lymphokine and SRBC to produce antibody are profoundly inhibited from producing PFC despite the absence of CsA in culture. These findings suggest that CsA has direct irreversible, fast acting inhibitory effects on B lymphocytes aside from or in addition to its effects on T cells.Department of BiologyThesis (M.S.