This project aims to continue investigation of a preclinical model of intestinal transplantation in inbred rats with the ultimate goal of making clinical intestinal transplantation a safe and effective treatment for short bowel syndrome in man. With the animal model we plan to determine if prolonged survival or tolerance of intestinal grafts can be produced without long term immunosuppression, by means of two new approaches to recipient pretreatment: enteral administration and portal vein injection of donor type cells combined with short-term cyclosporine. We plan to investigate if rejection of intestinal grafts can be detected before profound damage to graft or host has occurred, using three techniques: detecting the urinary excretion of low molecular weight polyethylene glycol which leaks from the rejecting bowel; measuring tissue levels of GI peptides and peptide receptors in the intestine; and measuring the expression of class II histocompatibility antigens on intestinal mucosa. Finally, we plan to investigate the mechanism of long-term tolerance of intestinal grafts by a variety of in vivo and in vitro techniques. These include adoptive transfer, mixed lymphocyte culture, and limiting dilution analysis cytotoxicity studies of lymphocytes obtained from tolerant hosts, and immunohistochemical staining. By these techniques we hope to determine the nature and time sequence of cellular and humoral responses which mediate tolerance of an intestinal allograft.
| Teitelbaum, D H; Sonnino, R E; Harmel Jr, R P (1996) Loss of intestinal integrity following small bowel transplant rejection in the rat. Transplant Proc 28:2547-8 |
| Sirinek, L P; O'Dorisio, M S; Dunaway, D J (1995) Accumulation of donor-specific cytotoxic T cells in intestinal lymphoid tissues following intestinal transplantation. J Clin Immunol 15:258-65 |
| Teitelbaum, D H; Sonnino, R E; Dunaway, D J et al. (1993) Rat jejunal absorptive function after intestinal transplantation. Effects of extrinsic denervation. Dig Dis Sci 38:1099-104 |
| Chen, F; O'Dorisio, M S; Hermann, G et al. (1993) Mechanisms of action of long-acting analogs of somatostatin. Regul Pept 44:285-95 |
| Sonnino, R E; Teitelbaum, D H; Harmel Jr, R P (1990) Cervical small bowel transplantation in the rat: a useful tool. Microsurgery 11:309-13 |
| Teitelbaum, D H; Dunaway, D J; Sonnino, R E et al. (1989) Leakage of intraluminal low molecular weight polyethylene glycol as a marker of small bowel transplant rejection. J Pediatr Surg 24:64-8;discussion 68-9 |
| Teitelbaum, D H; Wise, W E; Sonnino, R E et al. (1989) Monitoring of intestinal transplant rejection. Am J Surg 157:318-22 |
| Sonnino, R E; Teitelbaum, D H; Dunaway, D J et al. (1989) Small-bowel transplantation permits survival in rats with lethal short-gut syndrome. J Pediatr Surg 24:959-62 |
| Harmel Jr, R P; Tutschka, P J; Sonnino, R E et al. (1989) Immune tolerance of intestinal allografts in the rat. Transplant Proc 21:2883-4 |
| Teitelbaum, D H; O'Dorisio, T M; Qualman, S J et al. (1989) Alteration in gastrointestinal peptide tissue levels in rejecting small bowel transplants. J Pediatr Surg 24:629-33 |
