Abstract
Transferrin receptor (TfR) expression is up‐regulated during T cell activation after the interaction of the T cell receptor with the antigen‐major histocompatibility complex and the expression of interleukin‐2 (IL‐2) receptor. We hypothesize that anti‐TfR monoclonal antibody (mAb) will prolong allograft survival by altering T cell responses. In a murine heterotopic nonvascularized cardiac allograft model, CBA/J (H‐2k) recipients were transplanted with neonatal C57BL/6 (H‐2b) donor hearts. Anti‐TfR or isotype‐matched control mAbs (100 μg) were administered at the time of transplantation and on the following day. Splenocytes from naive CBA/J mice were stimulated in vitro with C57BL/6 alloantigen. Anti‐TfR mAb was administered at 5 μg/mL during the initiation of culture. Cytotoxic T lymphocyte (CTL) and mixed lymphocyte responses (MLR) were performed to assess T cell function. After 24 h in culture, cells were harvested, RNA isolated, and semi‐quantitative reverse transcriptase‐polymerase chain reaction performed. Anti‐TfR mAb prolonged allograft survival to 25.7 ± 0.9 days compared to the isotype control (10.7 ± 0.4 days, P < 0.01, Wilcoxon rank sum). Anti‐TfR mAb completely abrogated the CTL response and suppressed the MLR by 70–86% compared to the isotype controls. Anti‐TfR mAb suppressed IL‐2, interferon‐γ (IFN‐γ), IL‐10, and IL‐12 p40 mRNA expression, but had no effect on IL‐4, IL‐12 p35, and IL‐15 mRNA expression. In conclusion, anti‐TfR mAb prolongs allograft survival, suppresses T cell function, and alters IL‐2, IL‐10, IL‐12 p40, and IFN‐γ mRNA expression. These data suggest that the down‐regulation in IL‐12 mRNA by anti‐TfR mAb may prevent the development of T helper cells, thereby promoting graft survival and altering cell‐mediated immune responses. The partial effect by anti‐TfR mAb on cytokine mRNA expression may be due to other contributing factors such as costimulation. J. Leukoc. Biol. 64: 19–24; 1998.
