期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 12, 期 8, 页码 2017-2028出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1600-6143.2012.04073.x
关键词
Antibody-mediated rejection; animal models; basic science; biomarker; cardiac transplant; graft rejection; leukocyte infiltration; neutrophils
资金
- NIH [RO1 AI40459, PO1 AI087586]
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-2b) and B6.CCR5-/- recipients. Donor-specific antibody titers in CCR5-/- recipients were 30-fold higher than in wild-type recipients. B6.Kd 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.Kd allografts were rejected by CD8-/-/CCR5-/-, but not mu MT-/-/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-Kd 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.
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