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Antibody‐Mediated Rejection of Single Class I MHC‐Disparate Cardiac Allografts
Author(s) -
Hattori Y.,
Bucy R. P.,
Kubota Y.,
Baldwin III W. M.,
Fairchild R. L.
Publication year - 2012
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.1600-6143.2012.04073.x
Subject(s) - medicine , immunology , major histocompatibility complex , antibody , graft rejection , heart transplantation , transplantation , antigen
Murine CCR5 −/− recipients produce high titers of antibody to complete MHC‐mismatched heart and renal allografts. To study mechanisms of class I MHC antibody‐mediated allograft injury, we tested the rejection of heart allografts transgenically expressing a single class I MHC disparity in wild‐type C57BL/6 (H‐2 b ) and B6.CCR5 −/− recipients. Donor‐specific antibody titers in CCR5 −/− recipients were 30‐fold higher than in wild‐type recipients. B6.K d allografts survived longer than 60 days in wild‐type recipients whereas CCR5 −/− recipients rejected all allografts within 14 days. Rejection was accompanied by infiltration of CD8 T cells, neutrophils and macrophages, and C4d deposition in the graft capillaries. B6.K d allografts were rejected by CD8 −/− /CCR5 −/− , but not μMT −/− /CCR5 −/− , recipients indicating the need for antibody but not CD8 T cells. Grafts recovered at day 10 from CCR5 −/− and CD8 −/− /CCR5 −/− recipients and from RAG‐1 −/− allograft recipients injected with anti‐K d antibodies expressed high levels of perforin, myeloperoxidase and CCL5 mRNA. These studies indicate that the continual production of antidonor class I MHC antibody can mediate allograft rejection, that donor‐reactive CD8 T cells synergize with the antibody to contribute to rejection, and that expression of three biomarkers during rejection can occur in the absence of this CD8 T cell activity.