Loss of medullary dendritic cells in the thymus after cyclosporine and irradiation

Cyclosporine (CsA) induces a paradoxical graft-vs-host-like disease (GVHD) in syngeneic rat chimeras, providing the rat has a thymus and receives mediastinal irradiation. Here we evaluate the effect of CsA and irradiation on the relative abundance of thymic dendritic cells (DC). DC were identified with an immunoperoxidase stain for ED1 and were quantified by computerized planimetry. Normal young rats have scattered DC in the cortex and numerous DC in the medulla with a concentration at the cortico-medullary junction. Short-term CsA induces a marked loss of medullary DC (798 +/- 126 cells/mm to 88 +/- 103, P less than 0.001) and a modest loss of cortical DC (543 +/- 55 to 330 +/- 130, P less than 0.01). While medullary DC normally recover promptly post-CsA, rats receiving mediastinal irradiation demonstrated minimal recovery post-CsA (P less than 0.0003). The prolonged deficiency of medullary DC could represent an essential early step for loss of self-tolerance and sGVHD.