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Transpl Immunol. 1999 Sep;7(3):131-9.

Differential effects of transferrin receptor blockade on the cellular mechanisms involved in graft rejection.

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1
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, USA.

Abstract

Since transferrin receptor (TfR) appears on activated T cells following the interaction of the antigen-major histocompatibility complex (MHC) with the T cell receptor (TCR) and the appearance of interleukin (IL)-2R, we therefore hypothesize that in vivo blockade of TfR prolongs allograft survival by altering the cellular mechanisms involved in graft rejection. Previous results in our laboratory have demonstrated that anti-TfR monoclonal antibody (mAb) at 100 microg on days 0 and 1 of transplantation significantly prolonged allograft survival to 25.7 +/- 0.9 days in a murine heterotopic, nonvascularized cardiac allograft model. In the current studies, administration of anti-TfR mAb at the time of maximal TfR expression, on days 2 and 3 post-transplantation, failed to prolong allograft survival (13.0 +/- 0.0 days) compared to the isotype controls (10.5 +/- 0.5 and 10.7 +/- 0.4 days) (p < 0.01, Wilcoxon rank sum). A 4-day course of anti-TfR mAb significantly prolonged allograft survival compared to the isotype controls, but was no more effective than a 2-day course of the mAb. Anti-TfR mAb suppressed the mixed lymphocyte response to donor-specific and third-party alloantigen by 78.7% (p < 0.05) and 80.8% (p < 0.05), respectively, while stimulating the CTL response to donor-specific (16.3%, p < 0.05) and third party (49.3%, p < 0.01) alloantigen. Anti-TfR mAb suppressed IL-15 and increased IL-4 intragraft mRNA expression when compared to the isotype controls. Examination of cell surface receptors important during T cell activation revealed alterations in expression following anti-TfR mAb treatment. Anti-TfR mAb is an effective immunosuppressant prolonging allograft survival by altering cell-mediated immune responses and the intragraft cytokine micro-environment.

PMID:
10608296
[Indexed for MEDLINE]
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