Jgmc. Damoiseaux et al., MULTIPLE EFFECTS OF CYCLOSPORINE-A ON THE THYMUS IN RELATION TO T-CELL DEVELOPMENT AND AUTOIMMUNITY, Clinical immunology and immunopathology, 82(3), 1997, pp. 197-202
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.