Association of the CD134/CD134L costimulatory pathway with acute rejection of small bowel allograft

Background. The CD134/CD134L interaction provides a strong costimulatory signal that is CD28-independent. The CD134/CD134L pathway has been studied in inflammatory, autoimmune diseases, and graft-versus-host disease, but no information exists on the involvement of CD134/CD134L interactions in solid organ transplantation. Methods. CD134/CD134L costimulation was studied in a rat model of small bowel transplantation. Immunohistochemistry and flow cytometry were used to analyze the expression and localization of CD134/ CD134L. Mixed lymphocyte culture and quantitative RT-PCR were used to measure the effect on T proliferation and T helper cell cytokine transcripts of single or combined CD134 and CD28 costimulatory blockade. Results. CD134 and CD134L molecules were strongly expressed in acutely rejected small bowel allografts. This expression was significantly suppressed by FK506. Interruption of the CD134 and CD28 costimulatory pathways resulted in an pronounced increase in expression of interleukin-10 transcripts. Conclusion. These results present the first evidence that the CD134/CD134L interaction is associated with acute allograft rejection. Combined CD134/CD134L blockade may be an effective treatment to both prevent acute allograft rejection and promote the induction of cells with regulatory capacity.