IN VIVO REQUIREMENTS FOR NATURAL KILLER (NK) AND B CELLS IN CONCORDANT CARDIAC XENOGRAFT REJECTION

Abstract

1007 Purpose: Cellular mechanisms involved in vascularized concordant xenograft rejection remain controversial. We examined the role of NK and B cell-mediated immune responses in a newly described concordant cardiac xenotransplant model using the Chinese hamster (CH) as donor and NK and B cell knockout (KO) mice as recipients. Methods: For NK cell requirement, C57BL/6 Beige, and FasL and perforin double KO mice generated in our laboratory were used. To determine B cell requirement, μMT mice which are deficient in all subclasses of IgG and IgM, and BTK KO mice which lack IgM and IgG3 were used. Heterotopic auxillary cardiac transplantation was performed and the mean survival time (MST) was assessed by daily palpation. The production of mouse anti-CH antibody (Ab) was assessed by flow cytometry. Results:(Table)TableConclusion: The MST of concordant cardiac xenografts are modestly but statistically significantly prolonged in the absence of NK cell effector functions and IgG and IgM produced by B cells. Indefinite survival of the concordant cardiac xenografts in nude mice which have normal NK and T cell-independent B cell function suggests that T cell-dependent xenogeneic immune response is necessary and critical for the concordant xenograft rejection.