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