Significant role of intragraft lymphoid tissues in preventing insulin-dependent diabetes mellitus recurrence in whole pancreaticoduodenal transplantation.
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.
Tori
M
M
Division of Organ Transplantation, Department of Bioregulation, Biomedical Research Center, Osaka University Medical School, Osaka, Japan.
Ito
T
T
Yumiba
T
T
Maeda
A
A
Sawai
T
T
Miyasaka
M
M
Kiyono
H
H
Matsuda
H
H
Nozawa
M
M
Shirakura
R
R
D000818:Animals; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology* / Q000517:prevention & control*; D004386:Duodenum / Q000637:transplantation*; D007694:Killer Cells, Natural / Q000502:physiology; D008221:Lymphoid Tissue / Q000502:physiology*; D008297:Male; D016035:Pancreas Transplantation; D011183:Postoperative Complications / Q000503:physiopathology* / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D012008:Recurrence