Rejection of first-set skin allografts in man. the microvasculature is the critical target of the immune response.

Abstract

Recent reports of microvascular injury in delayed hypersensitivity skin reactions prompted a reexamination into the pathogenesis of 1st-set skin allograft rejection in man using morphologic techniques that allowed extensive vessel sampling and unequivocal evaluation of microvascular endothelium. Wide-spread microvascular damage was a characteristic, early consequence of the cellular immune response to 1st-set human skin allografts and was qualitatively similar to, but substantially more extensive than, that occurring in delayed hypersensitivity reactions. Microvascular damage invariably preceded significant epithelial necrosis and affected initially and primarily those venules, arterioles and small veins enveloped by lymphocytes. Vessels of the allograft itself and the underlying graft bed (recipient tissue) were equally affected. Endothelial cells of the microvasculature are apparently the critical target of the immune response in 1st-set vascularized skin allograft region in man and rejection may be attributed largely to ischemic infarction resulting from extensive microvascular damage. Other mechanisms, such as direct cellular contacts between infiltrating lymphocytes and epithelium, apparently played only a minor role. The rejection of 1st-set vascularized skin allografts, though induced by immunologically specific mechanisms, is apparently primarily effected by final pathways that are relatively nonspecific and that may cause damage to foreign and host vessels and cells. Rather than contradicting studies demonstrating the exquisite specificity of a allograft rejection in other systems, these findings provide a further example of the heterogeneity of the cellular immune response. Recognition of the critical role of immunologically mediated microvascular injury may prove important for an understanding of the biology of allograft rejection and for strategies aimed at prolonging allograft survival.