Effect of cyclosporine on T lymphocyte development: Relationship to syngeneic graft-versus-host disease

This report investigates the effects of cyclosporine on the reconstitution of T lymphocytes after syngeneic bone marrow transplantation and its role in the development of a novel T cell-mediated autoimmune disease, syngeneic graft versus host disease. We analyzed the effect of CsA treatment on T lymphocyte differentiation during reconstitution after bone marrow transplantation and correlated the maturation of CD4⁺and CD8⁺T cell subsets with the onset of syngeneic GVHD. Administration of CsA following syngeneic bone marrow transplantation leads to a developmental arrest of mature CD4⁺and CD8⁺T lymphocytes in the thymus and a marked reduction in cells expressing the αß T cell receptor. The reduction of CD4⁺and CD8⁺T cell subsets is also reflected in the peripheral lymphoid compartment with an altered CD4/CD8 ratio. Functional assessment of the cells revealed that CD8⁺cells respond normally to mitogenic signalling whereas CD4⁺cells exhibit marginal proliferative responses. Both subsets of T lymphocytes respond to syngeneic B lymphoblasts, comparable to the response of T lymphocytes from non-CsA-treated syn-geneic BMT recipients, suggesting that autoreactive cells are produced despite CsA treatment. Following discontinuation of CsA, T cell differentiation in the thy-mus is rapidly restored to normal. However, concurrent with the onset of syngeneic GVHD, a compensatory in-surgence of CD4⁺T helper cells is observed.