Cyclosporin A prevents the in vivo development of murine prothymocytes from uncommitted (Thy-1-) precursor cells

Cyclosporin A (CsA) is known to cause atrophy of the thymic medulla in normal mice. We show that medullary regeneration in lethally irradiated animals reconstituted with syngeneic marrow is also inhibited. For such animals, thymic cortical development is apparently normal. However, if the marrow is depleted of either Thy-1+ or Lyt-1+ cells, thymic regeneration is severely inhibited by CsA. This is not a permanent process, since thymic regeneration proceeds normally if the drug is withdrawn. CsA is only effective at preventing thymic regeneration if it is given at the time of grafting; after a delay of 3 days it is ineffective. We conclude that CsA inhibits the development of prothymocytes (pre-T cells) from common stem cells in the marrow. The significance of these findings with reference to T-cell ontogeny and clinical bone marrow (BM) transplantation is discussed.