Age-related factors in cyclosporine-induced syngeneic graft-versus-host disease: regulatory role of marrow-derived T lymphocytes

The effect ofthe recipient's age on the induction ofSGVHD appears in part to be related to the thymic function of mature animals and its relative resistance to CsA . Beschorner et al. (14) recently demonstrated a correlation between the age ofthe recipient receiving both mediastinal radiation and concomitant CsA therapy and the capacity of the thymus to regenerate its normal histologic integrity, post-CsA withdrawal . A prolonged disappearance of the medulla is more notable in immature rats than those of mature rats. There is an associated loss of medullary epithelium, Hassall's corpuscles, and class II antigen expression. Mature rats have a more prominent medulla before CsA therapy and hence are more resistant to thymic involution. Hassall's corpuscles disappear, however, the medulla still has fusiform epithelium, dendritic cells, and MHC class II antigen expression despite CsA therapy. It has been postulated that the loss ofthe thymic medulla and the marked reduction of MHC class II antigen expression by CsA treatment results in the abrogation ofclonal deletion mechanisms and the emergence ofself-reactive clones (8, 10, 19) . The relative resistance of the thymic medulla of mature animals to the effects of CsA (and the subsequent preservation of clonal deletion mechanisms) may account for the decreased ability to induce SGVHD in these animals. However, at present, we cannot exclude that the resistance of mature animals is, in fact, due to the ability to rapidly regenerate a thymic-dependent host resistance mechanism (see below).