T cells are necessary and critical for xenograft rejection in new concordant cardiac xenotransplant model.

Abstract

A new vascularized concordant xenotransplant model using the Chinese hamster as donor and mouse as recipient species is reported. This model takes advantage of the wealth of informative immune reagents and knockout and transgenic backgrounds available for the mouse. Heterotopic auxillary cardiac transplantation was performed. The mean survival time was assessed by daily palpation. Xenoreactive antibody production was measured by flow cytometry, and cardiac xenografts were examined by light microscopy. The tempo of xenograft rejection in this model is consistent with concordant species combination. IgM and IgG3 responses were not critical for the concordant xenograft rejection. Long-term survival (>100 days) of the concordant cardiac xenografts was observed without any immunosuppression in nude mice. Reconstitution of nude mice with CD3+ T cells induced the xenograft rejection in 5.7 days (P<0.01). This new concordant cardiac xenotransplant model demonstrates that T-dependent xenogeneic immune response is necessary and critical for the xenograft rejection.