Antibody-mediated rejection of single class i MHC-disparate cardiac allografts

Y. Hattori, R. P. Bucy, Y. Kubota, W. M. Baldwin, R. L. Fairchild

Research output: Contribution to journalArticlepeer-review

Abstract

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 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-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. Anti-class I antibodies induce graft expression of perforin, CCL5 and myeloperoxidase during antibody-mediated rejection of single class I MHC-disparate allografts in a mouse model.

Original languageEnglish (US)
Pages (from-to)2017-2028
Number of pages12
JournalAmerican Journal of Transplantation
Volume12
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • animal models
  • Antibody-mediated rejection
  • basic science
  • biomarker
  • cardiac transplant
  • graft rejection
  • leukocyte infiltration
  • neutrophils

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

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