Role of anti-donor antibody in the rejection of pig proislet xenografts in mice

CBA/H mice produced serum anti-pig IgG(1), IgG(2a), and IgG(2b) following xenotransplantation of pig proislets beneath the kidney capsule; anti-pig IgM was present as pre-existing antibody in the serum of normal CBA/H mice and was also produced in response to pig proislet xenografts, Serum anti-pig IgG(3) was not detected post-xenotransplantation. Rejection of pig proislet xenografts and the production of anti-pig IgG(1), IgG(2a), and IgG(2b) isotypes were CD4 T cell-dependent, The capacity for adoptively transferred hyperimmune CBA/H mouse anti-pig PBL serum to induce the rejection of intact pig proislet xenografts in CD4 T cell-depleted mice was dose dependent and correlated with markedly elevated levels of serum anti-pig IgG(3), Levels of anti-pig IgG(1), IgG(2a), IgG(2b), and IgM comparable to control mice acutely rejecting pig proislet xenografts and achieved following adoptive transfer of hyperimmune serum did not correlate with induced xenograft rejection, These findings suggest that anti-pig Ig isotypes produced during the conventional process of acute proislet xenograft rejection do not play a major role in mediating graft damage. The acute rejection of pig proislet xenografts in the absence of serum anti-pig Ig in mu MT-/-hosts confirmed that anti-pig antibody is not essential for proislet xenograft destruction.