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Lesions of T‐Cell‐Mediated Kidney Allograft Rejection in Mice Do Not Require Perforin or Granzymes A and B
Author(s) -
Halloran Philip F.,
Urmson Joan,
Ramassar Vido,
Melk Anette,
Zhu LinFu,
Halloran Brendan P.,
Bleackley R. Chris
Publication year - 2004
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00421.x
Subject(s) - perforin , granzyme , granzyme b , cytotoxic t cell , medicine , immunology , kidney , t cell , cd8 , pathology , immune system , biology , biochemistry , in vitro
Organ allograft rejection is strongly associated with the presence of alloreactive cytotoxic T cells but the role of cytotoxicity in the pathologic lesions is unclear. Previous studies showed that the principal lesions of kidney rejection – interstitial infiltration, tubulitis, and endothelial arteritis – are T‐cell‐dependent and antibody‐independent. We studied the role of cytotoxic granule components perforin and granzymes A and B in the evolution of the T‐cell‐mediated lesions of mouse kidney transplant rejection. By real‐time RT‐PCR, allografts rejecting in wild‐type hosts at days 5, 7, 21, and 42 showed massively elevated and persistent expression of perforin and granzymes A and B, but evolution of tubulitis and arteritis did not correlate with increasing granzyme or perforin expression. Allografts transplanted into hosts with disrupted genes for perforin or granzymes A and B showed no change in tubulitis, arteritis, or MHC induction. Thus the development of the histologic lesions diagnostic of T‐cell‐mediated kidney transplant rejection are associated with but not mediated by perforin or granzyme A or B. Together with previous graft survival studies, these results indicate that the granule‐associated cytotoxic mechanisms of T cells are not the effectors of T‐cell‐mediated allograft rejection.