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Intrinsic in vitro abnormalities in dendritic cell generation caused by non‐MHC non‐obese diabetic genes
Author(s) -
Prasad Simon J,
Goodnow Christopher C
Publication year - 2002
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.2002.01074.x
Subject(s) - nod , nod mice , dendritic cell , bone marrow , congenic , major histocompatibility complex , biology , immunology , t cell , microbiology and biotechnology , immune system , gene , genetics
Genes outside the MHC create a general susceptibility to autoimmunity in non‐obese diabetic (NOD) mice. In this study, we describe marked differences in dendritic cell generation, in vitro , caused by non‐MHC NOD genes. Bone marrow cells from NOD.H‐2 k mice cultured in vitro with GM‐CSF and IL‐4 generated a reduced yield of dendritic cells when compared to bone marrow cells from B10.H‐2 k mice. This was due to failure to pass through successive rounds of cell division and elevated levels of apoptosis in NOD.H‐2 k precursor cells. This aberrant response to GM‐CSF and IL‐4 was unique to the NOD.H‐2 k background when compared to bone marrow cells from other H‐2 k congenic strains, and coculture experiments showed that it was cell‐autonomous. Overall, the results described in this study demonstrate a striking effect of non‐MHC NOD genes on dendritic cell generation from myeloid precursors derived from the NOD.H‐2 k strain. These results identify a useful genetic model to explore the regulation of dendritic cell formation. Conceivably, the dysregulation of the dendritic cell system described here may contribute to the generalized defects in self‐tolerance in the NOD strain.