Morphology and immunohistochemistry of rat aortic grafts

Allotransplantation (TPL) of the abdominal aortic segments of BN donors was performed in 32 Lewis recipients with or without cyclosporin A (CyA) immun osuppression, and the vascular changes were compared to those of 10 syngene ic grafts (Lewis --> Lewis) and to the autologous rat aortae. The vessels w ere examined 2, 3, 4 and 5 months post TPL by light microscopy, the thickne ss of intima and media was measured morphometrically and the cell infiltrat ion of adventitia and intima was assessed semiquantitatively. Thirty-six ao rtae were examined by three-step enzyme immunohistochemistry (proof of sele cted differentiation, proliferation, cytoskeletal and connective tissue mat rix antigens). The adventitia displayed an intense focal and scattered mono nuclear cell infiltration; it was more discrete and focal in the intima. Th is cellularity persisted in the allografts but disappeared from the intima and was reduced in the adventitia of the isografts after Four and five mont hs. Disseminated ED1(+) activated macrophages were the most prominent popul ation of infiltrates whereas modest numbers of adventitial ED2(+) tissue ma crophages remained constant throughout the intervals examined. CD4(+) cells (focal and scattered) outnumbered (roughly twice) the scattered CDS' lymph ocytes; both these types were rare in the intima. Leukocyte invasion of the media was lacking (except for scarce isolated CD8(+) cells in some allogra fts). In syngeneic grafts the smooth muscle cells (SMC) of media remained i ntact and the intimal thickening was slight to absent (about 5 mu m) four a nd five months post TPL. On the other hand, the allograft media underwent s evere destructive changes (karyolysis, depletion of alpha-SMC actin, focal calcification and general thinning without rupture or aneurysm). The promin ent allograft intimal thickening (70-80 mu m) was due to the proliferation of longitudinally oriented myointimal cells (alpha-SMC actin, ED2, PCNA and Ki67(+)) and an increase in matrix substance (strong metachromasia and pos itivity of chondroitin-sulfate proteoglycan). The deposition of lipids rema ined discrete, without atheromatous plaques and mural thrombosis. All chang es were comparable in CyA-treated and untreated animals. Thus the main lesions of the allografts were (i) persistent mononuclear inf iltration chiefly in adventitia, (ii) destruction of medial SMC, and (iii) intimal thickening by proliferation of myointimal cells. At the postTPL int ervals examined the proliferation and intimal migration of medial SMC were not apparent and a morphological correlate of significant anti-medial-SMC c ytotoxic attack was lacking.