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.
Delemarre
F G
FG
Department of Immunology, Erasmus University, Rotterdam, The Netherlands. delemarre@immu.fgg.eur.nl
Simons
P J
PJ
de Heer
H J
HJ
Drexhage
H A
HA
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology*; D003911:Dextrans; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D010587:Phagocytosis; D010641:Phenotype; D051381:Rats; D011913:Rats, Inbred BB; D017208:Rats, Wistar; D013154:Spleen / Q000276:immunology* / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology*