Synergistic effects of alpha-1,2-fucosyltransferase, DAF, and CD59 in suppression of xenogenic immunological responses.

ABSTRACT

BACKGROUND: Previous studies showed that alpha-1,2-fucosyltransferase (HT), decay accelerating factor (DAF), and CD59 have an inhibitory effect on the immunological rejection of xenogenic transplantation. METHODS: To investigate their possible synergistic effects in suppression of heterogeneic transplantation, we produced transgenic mouse lines expressing human HT, DAF, and/or CD59 by the standard pronuclear injection approach. PCR and Southern blot were used to identify the transgenic founder lines. Flow cytometry confirmed the high-level expression of HT, DAF, or CD59 in the transgenic mice. RESULTS: The deposition of IgM, C3c, or C9 in the cardiac vascular endothelial cells of the HT, HT/CD59, and/or DAF multiple positive transgenic mice was markedly decreased. The survival time and function of the hearts of the co-transgenic mice were significantly longer and higher than that of the single HT-positive transgenic mice (P < 0.05). CONCLUSION: The mice co-expressing HT/DAF or HT/CD59 could resist the hyperacute rejection better than those expressing HT alone. It is feasible to use HT and C-reactive proteins co-transgenic tissues to resist hyperacute rejection and xenograft rejection.