Oral Feeding with Pig Peripheral Lymphocytes Decreases the Xenogeneic Delayed Type Hypersensitivity Reaction in Galactosyltransferase Knockout Mice.

Purpose. Oral tolerance induction has shown promising results in experimental allotransplantation models but is not well investigated in xenotransplantation. We investigated the possibility to induce tolerance against pig peripheral lymphocytes (pPBL) in galactosyltransferase knockout mice (gal -/-), which produce antibodies against Gal alpha 1-3Gal.Material and methods. Female (gal -/-) mice 6 to 8 weeks old weighing 35 to 40 g (n = 10) were fed orally every third day five times with 2 X 10(7) isolated, viable pPBL, or with phosphate-buffered saline (PBS) only (n = 7). They were then immunized subcutaneously on day 0 with a subcellular lysate from 4 X 10(7) isolated, viable pPBL. On day 13, 25 mu L of a subcellular lysate corresponding to 1 X 10(7) isolated, viable pPBL was injected in the right dorsal foot pad, and the delayed type hypersensitivity (DTH) reaction was calculated after 24 hours by subtracting the swelling response from 25 mu L PBS in the left footpad. Anti-Gal alpha 1-3Gal immunoglobulin IgG and IgM antibody titers were measured in the serum before oral feeding and at day 14.Results. The DTH reaction of the pPBL fed mice was 0.07 +/- 0.05 mm vs 0.57 +/- 0.23 mm for the controls (P < .001). No significant differences in anti Gal alpha 1-3 Gal IgG and IgM antibody titers were seen.Conclusions. This study demonstrates for the first time that oral delivery of pPBL can counteract the indirect T-cell reaction against xenogeneic subcellular antigens from pPBL. These observations warrant further investigation in immunologically modified mice and perhaps in primate models of xenotransplantation.