Burstein D, Mordes J P, Greiner D L, Stein D, Nakamura N, Handler E S, Rossini A A
Department of Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts 01655.
Diabetes. 1989 Jan;38(1):24-30. doi: 10.2337/diab.38.1.24.
Previous studies have shown that multiple transfusions of spleen cells from histocompatible nondiabetic donors prevent autoimmune diabetes mellitus in diabetes-prone (DP) BioBreeding/Worcester (BB/Wor) rats. In this study, a single transfusion of greater than or equal to 50 x 10(6) cells from either diabetes-resistant (DR) BB/Wor or Wistar-Furth (WF) rats substantially reduced the incidence of diabetes when given to DP rats 27 or 46 days old but not 61 days old. Transfusion and protection were associated with the appearance of RT6+ donor lymph node cells in recipient rats. In vivo depletion of RT6+ T-lymphocytes in 150-day-old protected animals did not produce diabetes. DR BB/Wor and WF spleen cells were equally efficacious when given either intraperitoneally or intravenously. Mitogen-activated spleen cells were relatively less effective than untreated cells. We conclude that BB rat diabetes can be prevented by one transfusion of spleen cells from histocompatible DR and WF donors, and that the protective effect is dependent on recipient age and cell dose. The effect may be mediated by a population of RT6+ T-lymphocytes that, during a critical developmental period, regulate the expression of autoimmunity in these animals.
先前的研究表明,给糖尿病易感性(DP)BioBreeding/Worcester(BB/Wor)大鼠多次输注来自组织相容性非糖尿病供体的脾细胞可预防自身免疫性糖尿病。在本研究中,给27日龄或46日龄而非61日龄的DP大鼠单次输注≥50×10⁶个来自抗糖尿病(DR)BB/Wor或Wistar-Furth(WF)大鼠的细胞,可显著降低糖尿病的发病率。输血和保护作用与受体大鼠中RT6⁺供体淋巴结细胞的出现有关。在150日龄受保护动物体内清除RT6⁺T淋巴细胞不会引发糖尿病。DR BB/Wor和WF脾细胞经腹腔或静脉注射给药时效果相同。有丝分裂原激活的脾细胞相对不如未处理的细胞有效。我们得出结论,给DP大鼠单次输注来自组织相容性DR和WF供体的脾细胞可预防BB大鼠糖尿病,且保护作用取决于受体年龄和细胞剂量。这种作用可能由一群RT6⁺T淋巴细胞介导,在关键的发育阶段,这群细胞可调节这些动物自身免疫性的表达。