Downregulation of immune response by the human cytokines Interleukin-32alpha and beta in cell-mediated rejection.

Xenotransplantation of porcine organs has the potential to help overcome the severe shortage of human tissues and organs available for human transplantation. However, numerous hurdles such as immune-mediated xenograft rejection remain before clinical xenotransplantation. In this study, we elucidated the role of human TNF-alpha-inducing factor, Interleukin-32 (IL-32), in porcine kidney cells (PK-15) during cell-mediated rejection by examining host cell responses. CD8+ and CD4+ T cells numbers were reduced in the lymph nodes of PK-15/IL-32beta injected mice. CD3+ Tcells were in mice injected with control cells but PK-15/IL-32alpha- and PK-15/IL-32beta-injected cell numbers were lower in lymph nodes than un transfected controls. In Mixed lymphocyte reaction cultures, the rates of cell proliferation were increased in both PK-15/IL-32alpha- and PK-15/IL-32beta-injected groups compared to the untransfected control groups. The Stable porcine PK-15 cells expression IL-32alpha and IL-32beta inhibited cytotoxic T lymphocyte (CTLs) after cellular xenograft. Our results suggest that human IL-32alpha and IL-32beta regulates on xenograft rejection in cellular xenotransplantation.