Signs of immaturity of splenic dendritic cells from the autoimmune prone biobreeding rat: consequences for the in vitro expansion of regulator and effector T cells
From the biobreeding-diabetic prone (BB-DP) rat, an animal model for endocrine autoimmunity, phenotype and function of splenic dendritic cells (DC) were studied. Furthermore, the suppressive effect of peritoneal macrophages (pMphi) from the BB-DP rat in the MLR was investigated. Lower numbers of splenic DC were isolated from BB-DP rats than from control Wistar rats. In the preautoimmune phase, DC of the BB-DP rat had a lower surface MHC class II expression (and in preliminary data, a lower CD80 expression), ingested more bacteria, and had a lower stimulatory potency in the syngeneic (syn)MLR as compared with control DC. During disease development, the MHC class II expression further decreased, and a low stimulatory activity became evident in the allogeneic (allo)MLR. With regard to the expansion of suppressor/regulatory T cells, a lower percentage of RT6+ T cells but higher percentages of CD45RClow T cells were induced by BB-DP DC in synMLR, but not in alloMLR. An increase in the CD4/CD8 T cell ratio was observed in both the syn- and alloMLR due to a relative weak expansion of CD8+ T cells with DC of the BB-DP rat. Resident pMphi isolated from BB-DP or Wistar rats were equally effective in suppressing the DC-driven synMLR. In conclusion, splenic DC from the BB-DP rat have a lower accessory cell function already at young age, before the development of disease, and expanded different subsets of effector/suppressor T cells in vitro as compared with those from Wistar rats. The dysfunction of DC from BB-DP rats is likely to be caused by their relative immaturity as indicated by their low class II and costimulatory molecule expression and relatively high phagocytic activity.
|Animals, Autoimmune Diseases/*immunology/*pathology, Cell Differentiation, Dendritic Cells/*immunology/*pathology, Dextrans, Diabetes Mellitus, Type 1/immunology/pathology, Escherichia coli/immunology, Female, Fluorescein-5-isothiocyanate/analogs & derivatives, Histocompatibility Antigens Class II/metabolism, In Vitro, Lymphocyte Activation, Lymphocyte Culture Test, Mixed, Macrophages, Peritoneal/immunology, Male, Phagocytosis, Phenotype, Rats, Rats, Inbred BB, Rats, Wistar, Research Support, Non-U.S. Gov't, Spleen/*immunology/*pathology, T-Lymphocyte Subsets/*immunology/*pathology|
|Journal of Immunology|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Delemarre, F.G, Simons, P.J, de Heer, H.J, & Drexhage, H.A. (1999). Signs of immaturity of splenic dendritic cells from the autoimmune prone biobreeding rat: consequences for the in vitro expansion of regulator and effector T cells. Journal of Immunology. Retrieved from http://hdl.handle.net/1765/9012