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Department of Immunology, Erasmus University, Rotterdam, The Netherlands
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 (pM
) 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 pM 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.
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