Study on systemic immune tolerance induction in rat islet transplantation by intravenous infusion of Sertoli cells

Abstract

Background: Sertoli cells are usually co-transplanted with pancreatic islets to induce local immune tolerance. In this report, we used infusion with Sertoli cells in islet transplantation to induce systemic immune tolerance and studied the mechanism of the tolerance induction.

Methods: Streptozotocin-induced diabetic rats were divided into four groups before islet transplantation: group A as control; group B with intravenous infusion of Sertoli cells; group C with Sertoli cell infusion and Fas ligand antibody treatment; and group D with Sertoli cell infusion and transforming growth factor-beta1 antibody treatment. The mean survival time (MST) and insulin expression of islet grafts were measured. The number of lymphocytes and the levels of cytokines in peripheral blood were also measured.

Results: Group B had the longest MST of islet allografts (41.6+/-4.20 days) followed by groups C, D, and A (P<0.05). Immunohistochemistry showed similar results with MST. The rats in group B had the least CD4 T cells (only 15.6%+/-6.4%) compared with other groups (P<0.05). The numbers of CD8 T cells in rats of groups B (11.2%+/-4.3%) and D (14.5%+/-5.6%) were significantly lower than those of groups A and C (P<0.05). After transplantation, group B's interleukin (IL)-2 level (1.92+/-0.68 ng/mL) was found to be significantly lower than that of other groups (P<0.05). Interferon-gamma showed similar pattern of change as IL-2 (P<0.05). Groups A and D had significantly lower levels of IL-4 (4.31+/-1.97 pg/mL 4.69+/-1.33 pg/mL, respectively) than groups B and C (P<0.05).

Conclusion: Infusion of Sertoli cells could effectively prolong the survival of islet grafts and reduce peripheral blood lymphocyte and cytokine levels. In this process, transforming growth factor-beta1 played a major role and Fas ligand played a smaller additional role.