Significant role of intragraft lymphoid tissues in preventing insulin-dependent diabetes mellitus recurrence in whole pancreaticoduodenal transplantation

Abstract

Graft recurrence of insulin-dependent diabetes mellitus (IDDM) was examined. Islet transplantation or pancreas-alone transplantation excluding the duodenum and peripancreatic lymph nodes was compared with whole pancreaticoduodenal transplantation. A Wistar Furth (WF; RT1(u), RT6.2) to major histocompatibility complex (MHC)-compatible diabetes-prone (DP; RT1(u), RT6.1 gene carrier)-biobreeding (BB) rat transplantation model was used. Only DP recipients that had been transplanted with whole pancreaticoduodenal grafts were free from IDDM recurrence (>60 days postgrafting) when treated with anti-intercellular adhesion moluecule-1 (ICAM)-1/leukocyte function-associated antigen-1 (LFA-1) monoclonal antibodies (mAbs). In the spleen cells of the DP rats that had accepted pancreatic grafts (60 days postgrafting), flow cytometric analysis showed that NKR-P1(+)TCRalphabeta(+) (NKT) cells had proliferated markedly, with the proportion of 12.8 +/- 1.7% in the total splenic T cells, most of which (86.2%) were derived from the donor (RT6.2(+)). By enzyme-linked immunonosorbent assay (ELISA), serum interferon gamma (IFN-gamma) was not detected (<13 pg/ml) in all rats. However, interleukin-4 (IL-4) was detected as 158.8 +/- 28.0 pg/ml in the nonrecurrent DP recipients. These data suggested that to prevent IDDM recurrence in the pancreatic graft, the lymphocytes in the pancreaticoduodenal grafts are necessary. Also, the donor-derived NKT cells might have some immunoregulatory functions with a Th2 deviation.

Experimental rodent models of prostatitis: limitations and potential

“…153 Upon activation, NKT cells produce large amounts of IFN-g and IL-4 154 and play an important role in rat autoimmunity 155,156 NKT cells have been shown to have immunoregulatory functions with a Th2 type immune response deviation in the Wistar-Furth rat whole pancreaticoduodenal transplantation model. 157 Of note, in young Sprague-Dawley rats which are resistant to spontaneous prostatitis, 67 the intraprostatic lymphocytes are almost equally divided between NK cells and NKT cells, whereas in similarly aged Wistar rats NK cells predominate. 150,151 CD45RC À CD4 þ T cells have been termed regulatory T cells because of their ability to prevent autoimmune thyroiditis and diabetes in rats.…”