LEW-TO-F344 CAROTID-ARTERY ALLOGRAFTS - ANALYSIS OF A RAT MODEL OF POSTTRANSPLANT VASCULAR INJURY INVOLVING CELL-MEDIATED AND HUMORAL RESPONSES

A key manifestation of chronic rejection is an obliterative arterioscl erosis, Myointimal thickening in the vessel is preceded by an endothel ialitis involving accumulation of host mononuclear cells in the periva scular and intimal spaces, We report a paratopic LEW-to-F344 rat carot id artery transplantation model developed to study the cells, cytokine s, and inflammatory response associated with this early phase of vascu lar immune injury, Compared with contralateral control arteries and is ografts, LEW-to-F344 carotid allografts develop intimal thickening wit h mononuclear cell infiltration that persists (days 20, 45, 75, 90, an d 120). Allografted vessels had dense collections of intimal and adven titial leukocytes (CD45+) consisting of equal numbers of T cells and m acrophages, There were small but variable numbers of intimal smooth mu scle cells, Intimal cells showed dense staining for tumor necrosis fac tor-alpha, interleukin-8, platelet-derived growth factor, iNOS, and IC AM and weaker labeling for interleukin-1 beta and interleukin-6, There was also prominent staining for interleukin-4 and interleukin-7 with no detectable interferon-gamma or interleukin-alpha staining and high titer labeling for IgG1 (but not IgG2). The predominance of the T cell infiltrate coupled with interleukin-4 and IgG1 expression in carotid allografts is consistent with a TH2 response. This contrasts with ball oon-injured rat carotids, which evoke a macrophage-dependent prolifera tive response, These findings demonstrate that there are distinct as w ell as common activation pathways in various forms of vascular injury and the LEW-to-F344 carotid model provides the opportunity to gain ins ight into molecular mechanisms regulating alloimmune injury in the ves sel.