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

ABSTRACT

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.