CYCLOSPORINE-A-INDUCED AUTOIMMUNITY - THE RESULT OF DEFECTIVE DE-NOVOT-CELL DEVELOPMENT

Cyclosporin A-induced autoimmunity (CsA-AI) is an autoimmune disease, caused by the combinatory treatment with irradiation and cyclosporin A (CsA). CsA-AI is the result of defective T-cell maturation leading to disturbed T-cell balances in the periphery, Increases in Th1 cells an d reduction of autoregulatory cells eventually enable the enumerated a utoreactive CD4 and CD8 T cells to disturb the homeostasis in the targ et organs, In unravelling the effect of CsA on T-cell maturation and t he role of T cells in CsA-AI many pieces have been put in their places ; nevertheless, some remain the topic of debate, The identity of the a utoantigen(s) remains elusive, the working mechanism of the autoregula tory cells still is to be determined, and the interplay between CD4 an d CD8 T-cell subsets in relation to type-1 and type-2 responses is a m atter of interest. In spite of all these unknowns, the CsA-AI autoimmu ne model is, in contrast to many autoimmune models induced by immuniza tion with a foreign protein in adjuvant, an interesting physiological model based on defective T-cell development including aberrant selecti on in the thymus and disturbed T-cell balances in the periphery.