Evidence for cooperativity in the rejection of cardiac grafts mediated by CD4+ TCR Tg T cells specific for a defined allopeptide

Academic Article

Abstract

  • Understanding the mechanisms of rejection of organs transplanted between unrelated individuals is confounded by the complexity of the alloantigens and the diversity of T cells responding to these alloantigens. To circumvent these problems, we developed a transgenic (Tg) C57BL/6 model system in which the T-cell receptor (TCR) expressed by CD4 T cells is specific for a defined allogeneic H-2Kd peptide and the cardiac donor expressed H-2K d as a transgene on the C57BL/6 background (B6.Kd). These TCR Tg T cells were previously shown to mediate rapid rejection of a B10.D2 cardiac allograft when transferred to Rag1 recipients, demonstrating that the "indirect" pathway of allorecognition is sufficient for complete rejection in the absence of other T cells or antibody. Here, we report that B6.Kd hearts were rejected in an accelerated fashion by Rag1 -/- TCR Tg T cells adoptively transferred to normal B6 recipients. Rejection in this model was associated with large myocardial infarcts and significant coronary artery inflammation. Moreover, transferred TCR Tg CD4+ cells mediated allograft injury without the requirement for cytotoxic function from recipient-derived CD8 T cells. A non-linear relationship was observed between the initial precursor frequency of the antigen-specific TCR Tg cells and the ultimate tempo of acute rejection, which is taken as evidence for cooperativity between components of the system.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Honjo K; Xu XY; Kapp JA; Bucy RP
  • Start Page

  • 1762
  • End Page

  • 1768
  • Volume

  • 4
  • Issue

  • 11