IN-VITRO MODULATION OF HUMAN, AUTOREACTIVE MBP-SPECIFIC CD4-CELL CLONES BY CYCLOSPORINE-A( T)

Cyclosporin A (CsA) is a potent immunosuppressant affecting many compo nents of cellular and humoral immunity. Its main action probably resul ts from inhibition of T-lymphocyte activation and interference with se cretion of cytokines like IL-2, IL-4, IFN-gamma and TNF-alpha. Corresp ondingly, CsA has beneficial effects on the course of several autoimmu ne diseases thought to be mediated by T-lymphocytes, including a mild effect on multiple sclerosis. We exposed CD4(+) cytotoxic T-lymphocyte s specific for myelin basic protein, a putative target autoantigen in MS, to CsA in vitro, and determined the drug's effects on proliferatio n, expression of high affinity IL-2R, secretion of the proinflammatory cytokines IFN-gamma and TNF-alpha as well as on the secretion of the chemokines MIP-1 alpha and MIP-1 beta. In all instances, we observed a partial to complete inhibition. In contrast, the response of activate d cells to IL-2 was resistant to CsA. Our observations are in line wit h results obtained in different experimental systems. The discrepancy between the profound inhibition of T-cells and the modest therapeutic effects on MS is discussed.