Neonatal pig islets induce a lower T-cell response than adult pig islets in IDDM patients

Background. Pancreatic pig islets may provide a substitute in the future fo r difficult to obtain human islets for transplantation in insulin-dependent diabetes millitus (IDDM) patients. However, the immune response to xenogra fts may significantly hamper this approach. Because neonatal tissue is beli eved to be Less immunogenic, we examined whether the T-cell response to neo natal pig islets differs from the response Lo adult islets. Methods. The T-cell proliferative response to different concentrations of s onicated neonatal and adult pig islets, as well as to insulin and mitogens, was tested in 21 recent onset IDDM patients and 21 healthy controls. We de termined the presence of various circulating islet autoantibodies and their association with the T-cell response in IDDM patients. Results. In the IDDM patients, sonicated adult pig islets (at 1 mu g protei n/ml) induced a significantly higher frequency (12 of 21 vs. 1 of 21, p<0.0 01) and magnitude (2.58+/-0.44 vs. 1.38+/-0.13, p <0.02) of positive T-cell responses than neonatal islets at the same concentration. Similar results were obtained with a 10-fold higher concentration of islet sonicate. There was no significant association between the individual T-cell responses and the presence of circulating autoantibodies in IDDM patients. Conclusion. These results indicate that neonatal pig islets induce a lower T-cell reactivity than adult islets, suggesting that the neonatal tissue ma y be immunologically more suitable for future islet xenotransplantation.