Perturbation of T-cell differentiation in lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporin-A.

Lethally irradiated rats reconstituted with syngeneic bone marrow and treated for 40 or 80 days with Cyclosporin A (Cy-A) contract disease mimicking graft-versus-host disease about 3 weeks after withdrawal of the drug. We investigated the reconstitution of peripheral blood lymphocytes after this treatment. A selective effect on the regeneration of the CD4+ cells was observed. During Cy-A administration CD4(+)-cell regeneration was almost completely suppressed, but within 3 weeks after withdrawal of the drug such cells reappeared in blood and reached pre-irradiation levels about 6 weeks later. The coincidence of the reappearance of CD4+ cells and the onset of autoimmune disease suggests a causal relation between both events.