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Marked mitigation of transplant vascular sclerosis in FasLgld (CD95L) mutant recipients. The role of alloantibodies in the development of chronic rejection.

Abstract：

BACKGROUND:In the acute rejection of allografts, the interaction between Fas (CD95) and its ligand (FasL; CD95L) has been shown to be involved in mediating apoptotic cell death. The role, however, of these molecules in the pathogenesis of transplant vascular sclerosis is as yet undetermined. The present study was therefore designed to address this issue. MATERIAL:C3H/HEJ FasLgld (FasL-; H2k) spontaneously mutant mice were used either as donors or recipients of aortic allografts; wild-type C57B1/6 (B6; H2b) were used as corresponding recipients or donors (n=6/group), respectively. Controls included aortas transplanted across appropriate allogeneic and syngeneic strain combinations. For histopathological evaluations, the grafts were harvested at day 40 after transplantation, at which time, splenocytes and sera were also obtained for mixed leukocyte reaction and complement-mediated microcytotoxicity assays, respectively. RESULTS:Similar to aortas obtained from allogeneic controls, allografts harvested from FasL- -->B6 recipients had morphological evidence of chronic rejection characterized by circumferential intimal thickening with partial disruption of the elastic membranes. Correspondingly, heightened antidonor cellular reactivity was also witnessed in these recipients. On the contrary, B6 allografts harvested from the majority of C3H-->FasL- recipients exhibited marked preservation of aortic morphology. Although these recipients had diminished antidonor cellular proliferation, the titers of alloantibodies were markedly elevated. CONCLUSION:The presence of FasL-expressing functional cytotoxic T cells is required for the pathogenesis of transplant vascular sclerosis. The significant reduction and/or absence of chronic rejection with the concomitant retention of antidonor humoral response in C3H FasL- recipients of B6 aortas prompt us to suggest that perhaps posttransplantation vasculopathy is initiated by cell-mediated cytotoxicity with its perpetuation facilitated by alloantibodies.

journal_name

Transplantation

journal_title

Transplantation

authors

Subbotin V,Sun H,Aitouche A,Salam A,Valdivia LA,Fung JJ,Starzl TE,Rao AS

doi

10.1097/00007890-199905270-00001

subject

Has Abstract

pub_date

1999-05-27 00:00:00

pages

1295-300

issue

eissn

0041-1337

issn

1534-6080

journal_volume

pub_type

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Marked mitigation of transplant vascular sclerosis in FasLgld (CD95L) mutant recipients. The role of alloantibodies in the development of chronic rejection.