Donor-specific tolerance induced by simultaneous allogeneic islet transplantation with CD4+CD25+ T-cells into hepatic parenchyma in mice.
BACKGROUND
The allogeneic islets transplantation is an ideal therapeutic strategy for patients with diabetes mellitus. However, it has been difficult to induce immunological tolerance against islets grafts. The CD4+CD25+ regulatory T-cells (Treg) play a role in suppressing T-cell activation. Thus, we evaluated whether Treg can regulate donor-specific T-cell tolerance that received allogeneic islets into the hepatic parenchyma (ITxHP) along with Treg.


METHODS
C3H/He mice were used as donors; and streptozotocin-induced diabetic BALB/c mice were recipients. The protocol included three groups: Group A recipients received only 300 IE islets; Group B was given 300 IE islets and whole splenocytes; Group C was given 300 IE islets and Treg purified from peripheral lymph nodes.


RESULTS
For all mice in Groups A and B, the fasting blood sugar exceeded 250mg/dl and graft rejection was observed. GVHD was observed earlier in Group B than in Group A. In contrast graft survival exceeded 30 days for two mice in Group C (50%, mean POD 28.5 +/- 24.0, P<0.05). Mixed lymphocyte reaction showed that T-cells from tolerant mice had very weak responses against spleen cells from C3H mice.


CONCLUSIONS
The simultaneous ITxHP with CD4+CD25+ T-cells administration prolonged islet graft survivals and induced donor-specific hyporesponsiveness.
Ikemoto
Tetsuya
T
Department of Digestive and Pediatric Surgery, The University of Tokushima School of Medicine, Tokushima, Japan.
Tashiro
Seiki
S
Yasutomo
Koji
K
Kishihara
Kenji
K
Kurita
Nobuhiro
N
Miyake
Hidenori
H
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation*; D003920:Diabetes Mellitus / Q000601:surgery; D006085:Graft Survival; D006801:Humans; D007108:Immune Tolerance; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000601:surgery; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D014019:Tissue Donors; D014184:Transplantation, Homologous