BACKGROUND: Xenotransplantation seeks to have cells with discordant genotypes co-exist. The hypothesis that host genotype modulates xenogeneic immune response (IR) was tested. METHODS: Two inbred rat strains [Dark Agouti (DA) and Lewis (LEW)] representing diverse IR phenotypes were immunized with porcine blood mononuclear cells (BMC). Delayed-type hypersensitivity (DTH), immunoglobulin (Ig), antibody (Ab) and isotype bias of Ab response were evaluated. RESULTS: DTH to pig BMC was greater in DA than in LEW rats. Natural Ab was qualitatively different between strains (IgM and IgA predominated in DA, IgM and IgG(2a) predominated in LEW). Twice as much IgG was elicited from DA than LEW rats and DA utilized all isotypes whereas LEW did not use IgG(2a) or IgG(2c). IR bias was diametrically opposed; type 1 in DA but type 2 in LEW. Strains even differed in Ig profiles and dermal responses to saline injections and mitogen. The DA rats were the higher responders to pig BMC. CONCLUSIONS: Recipient genotype had significant and broad effects on IR to porcine BMC and may influence xenograft rejection and xenotolerance induction. Moreover, this study suggests that caution should prevail when interpreting data derived from a single inbred strain, particularly given that humans, the target species, are genetically diverse.
BACKGROUND: Xenotransplantation seeks to have cells with discordant genotypes co-exist. The hypothesis that host genotype modulates xenogeneic immune response (IR) was tested. METHODS: Two inbred rat strains [Dark Agouti (DA) and Lewis (LEW)] representing diverse IR phenotypes were immunized with porcine blood mononuclear cells (BMC). Delayed-type hypersensitivity (DTH), immunoglobulin (Ig), antibody (Ab) and isotype bias of Ab response were evaluated. RESULTS: DTH to pigBMC was greater in DA than in LEW rats. Natural Ab was qualitatively different between strains (IgM and IgA predominated in DA, IgM and IgG(2a) predominated in LEW). Twice as much IgG was elicited from DA than LEW rats and DA utilized all isotypes whereas LEW did not use IgG(2a) or IgG(2c). IR bias was diametrically opposed; type 1 in DA but type 2 in LEW. Strains even differed in Ig profiles and dermal responses to saline injections and mitogen. The DA rats were the higher responders to pigBMC. CONCLUSIONS: Recipient genotype had significant and broad effects on IR to porcine BMC and may influence xenograft rejection and xenotolerance induction. Moreover, this study suggests that caution should prevail when interpreting data derived from a single inbred strain, particularly given that humans, the target species, are genetically diverse.