Cell‐intrinsic effects of non‐MHC NOD genes on dendritic cell generation in vivo

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Abstract
Genes outside the MHC create a general susceptibility to autoimmunity in non‐obese diabetic (NOD) mice. Here we describe marked differences in dendritic cell generation in vivo, caused by non‐MHC NOD genes. Analyses of splenic dendritic cells from the autoimmunity‐prone NOD.H‐2k mice revealed a relative over‐representation of the CD8α– subsets, in contrast to the level of these subsets observed in the autoimmunity‐resistant B10.H‐2k congenic strain or other H‐2k strains. The imbalance towards CD8α– dendritic cells was selectively manifested by NOD.H‐2k‐derived cells in radiation chimeras reconstituted with equal mixtures of NOD.H‐2k and B10.H‐2k bone marrow cells. In addition to the cell‐intrinsic imbalance in dendritic cell subsets, the myeloid lineage overall was intrinsically altered by NOD genes, as this lineage was disproportionately derived from the NOD.H‐2k donor in mixed chimeras. These results identify a striking effect of non‐MHC NOD genes upon the balance of dendritic cell subsets that may contribute to the generalized defects in self‐tolerance in the NOD strain.