The effects ofin vivocyclosporin A administration on rat thymic dendritic cells

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Abstract
SUMMARY: Cyclosporin A (CsA) induces a graft-versus-host-like disease (GVHD) in lethally irradiated Lewis rats reconstituted with syngeneic bone marrow. The role of the thymus in the generation of disease has been unequivocally established. It has been suggested that the CsA-induced disappearance of thymic dendritic cells (DC) is responsible for the generation of the autoaggressive cells. In this study we quantify the loss of DC upon in vivo CsA administration in normal and bone marrow-reconstituted rats using an isolation technique. The phenotype of the DC is determined using MoAbs recognizing antigens which are expressed on thymic medullary DC. Furthermore, the functional aspects are assessed by determining the antigen presentation capacity. Short-term CsA exposure clearly affects the number of DC isolated from the thymus in a concentration-dependent manner. However, in all instances a substantial number of DC can be isolated from CsA-treated animals. These isolated DC exhibit an identical phenotype and function as DC isolated from control animals. Therefore, the partial deficiency of DC can not be held as essential for loss of tolerance.