Murine xenogeneic immune responses to the human testis: A presumed immune-privileged tissue

Introduction. Immune privilege provides a natural paradigm for potentially down-regulating allogeneic and xenogeneic inflammatory immune responses. Fa s ligand has been suggested as a general underlying mechanism of immune pri vilege; the human Fas ligand has been shown to ligate murine Fas in vitro. Methods. In this study, we examined whether the human testicular xenograft, a presumed immune-privileged tissue would have prolonged survival in mice. In addition, in vitro and in vivo murine xenogeneic immune responses to th e human testicular xenografts were characterized using MHC class I, MHC cla ss II, CD4, CDS, CD4/8 knockout mice. Results. Unlike in rodent testis, Fas ligand mRNA is not expressed and Fas is highly expressed in human testis, Human testicular xenografts are immuno genic, and do not induce any preferential pattern of recipient systemic Th1 or Th2 cytokine bias. Interestingly, an indefinite survival of the human t esticular xenografts is observed in murine MHC class II knockoutmice, where as the human skin xenografts were rejected without a delay. In vivo murine immune responses to human testicular xenografts require a recipient MHC cla ss II-dependent CD4 T cell-mediated process that appears to depend on B7-1/ B7-2 costimulatory signals. Conclusions. Our results demonstrate that the concept of immune privilege, as defined by the expression of Fas ligand and prolonged survival after tra nsplantation, cannot be extended to human testis, The stringent restriction of murine xenogeneic immune responses to discordant human testicular xenog rafts to the indirect MHC class II-dependent CD4 T cell-mediated pathway su ggests a potential venue for immune modulation to induce tolerance across a discordant species barrier.