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

被引:31
作者
Prasad, SJ [1 ]
Goodnow, CC [1 ]
机构
[1] Australian Natl Univ, Med Genome Ctr, John Curtin Sch Med Res, Canberra, ACT 0200, Australia
关键词
autoimmune diabetes; dendritic cell subsets; H-2 congenic NOD mice; myeloid precursors; non-MHC NOD genes;
D O I
10.1093/intimm/dxf034
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-2(k) mice revealed a relative over-representation of the CD8alpha(-) subsets, in contrast to the level of these subsets observed in the autoimmunity-resistant B10.H-2(k) congenic strain or other H-2(k) strains. The imbalance towards CD8alpha(-) dendritic cells was selectively manifested by NOD.H-2(k)-derived cells in radiation chimeras reconstituted with equal mixtures of NOD.H-2(k) and B10.H-2(k) 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-2(k) 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.
引用
收藏
页码:677 / 684
页数:8
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