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Publication : Dissociation of mouse cardiac transplant rejection and donor alloantigen-specific T cell responsiveness.

First Author  Bishop DK Year  1995
Journal  Transpl Immunol Volume  3
Issue  3 Pages  222-8
PubMed ID  8581410 Mgi Jnum  J:32672
Mgi Id  MGI:80161 Doi  10.1016/0966-3274(95)80028-x
Citation  Bishop DK, et al. (1995) Dissociation of mouse cardiac transplant rejection and donor alloantigen-specific T cell responsiveness. Transpl Immunol 3(3):222-8
abstractText  Mouse hearts transplanted into MHC disparate donors are usually rejected 1 week after placement. It is widely accepted that alloantigen-reactive helper T lymphocytes (HTL) and cytotoxic T lymphocytes (CTL) are the key mediators of acute allograft rejection. This report demonstrates that the presence or absence of 'traditional' graft-reactive HTL and CTL is not necessarily related to allograft survival. In these studies, donor/recipient combinations disparate only at MHC or only at minor histocompatibility (mH) loci were employed. Allograft survival was monitored, donor-reactive IL-2 (interleukin-2) producing HTL and CTL were quantified by modified limiting dilution analysis, and serum levels of cytolytic alloantibody were determined. C57BL/10 hearts (H-2b) transplanted into B10.BR (H-2k) recipients (full MHC disparity) enjoyed prolonged survival despite massive infiltration of the allograft by donor-reactive HTL and CTL. IgM, but not IgG, donor-reactive alloantibody was present in the sera of these mice. Hence, traditional IL-2 producing HTL and CTL were not capable of mediating acute graft rejection, nor of providing help for alloantibody isotype switching in this MHC disparate combination. In contrast, C3H/HeN (H-2k) hearts transplanted into B10.BR (H-2k) recipients (mH disparity only) were acutely rejected. Donor-reactive HTL and CTL were rare or not detectable in these recipients, and cytolytic alloantibody was not detectable. Similar observations were made when B10.BR hearts were transplanted into C3H/HeN recipients. Interestingly, treatment of recipients with anti-CD4 monoclonal antibody prevented rejection of mH disparate allografts. Therefore, CD4+ T cells were required for rejection of mH disparate allografts, but this process was independent of detectable IL-2 production or CTL function. Hence, the significance of monitoring 'traditional' T cell functions should be questioned in certain donor/recipient combinations.
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