MULTIPLE EFFECTS OF CYCLOSPORINE-A ON THE THYMUS IN RELATION TO T-CELL DEVELOPMENT AND AUTOIMMUNITY

The immunosuppressive reagent paradoxically is able to generate Cyclos porin A is known to interfere with the signal transduction upon T-cell receptor cross-linking, an event required not only for T-cell activat ion in the periphery but also for T-cell maturation and selection in t he thymus. In this review the multiple effects of cyclosporin A an the thymus are explained in terms of a differential response of thymocyte subsets upon recognition of MHC-peptide complexes. This hypothesis ho lds the effects of cyclosporin A on the thymic stromal cells to be sec ondary to its effect on the thymocytes: generation of autoreactive cel l's is the result of direct interference with negative selection and i s not due to the partial disappearance or alteration of thymic stromal cells and, depending on the concomitant reestablishment of the autore gulatory T-cell circuit in the periphery, autoimmunity may develop. (C ) 1997 Academic Press.