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 endocr ine autoimmunity, phenotype and function of splenic dendritic cells (DC) we re studied. Furthermore, the suppressive effect of peritoneal macrophages ( pM phi) from the BB-DP rat in the MLR was investigated. Lower numbers of sp lenic DC were isolated from BB-DP rats than from control Wistar rats. In th e preautoimmune phase, DC of the BB-DP rat had a lower surface MHC class Pi . expression (and in preliminary data, a lower CD80 expression), ingested m ore bacteria, and had a lower stimulatory potency in the syngeneic (syn)MLR as compared with control DC. During disease development the MHC class II e xpression further decreased, and a low stimulatory activity became evident in the allogeneic (allo)MLR. With regard to the expansion of suppressor/reg ulatory T cells, a lower percentage of RT6(+) T cells but higher percentage s of wCD45RC(low) T cells were induced by BB-DP DC in synMLR, but not in al loMLR. 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 pM phi isolated from BB-DP or Wistar rats were equ ally 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 Wister rat s. The dysfunction of DC from BB-DP rats is likely to be caused by their re lative immaturity as indicated by their low class II and costimulatory mole cule expression and relatively high phagocytic activity.