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Intrinsic in vitro abnormalities in dendritic cell generation caused by non-MHC non-obese diabetic genes

Prasad, S; Goodnow, Christopher

Description

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-2k 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-2k mice. This was due to failure to pass through successive rounds of cell division and elevated levels of...[Show more]

dc.contributor.authorPrasad, S
dc.contributor.authorGoodnow, Christopher
dc.date.accessioned2015-12-13T23:40:43Z
dc.identifier.issn0818-9641
dc.identifier.urihttp://hdl.handle.net/1885/94588
dc.description.abstractGenes 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-2k 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-2k mice. This was due to failure to pass through successive rounds of cell division and elevated levels of apoptosis in NOD.H-2k precursor cells. This aberrant response to GM-CSF and IL-4 was unique to the NOD.H-2k background when compared to bone marrow cells from other H-2k 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-2k 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.
dc.publisherBlackwell Publishing Ltd
dc.sourceImmunology and Cell Biology
dc.subjectKeywords: granulocyte macrophage colony stimulating factor; interleukin 4; animal cell; apoptosis; article; bone marrow cell; cell culture; cell division; congenic strain; controlled study; dendritic cell; diabetes mellitus; gene control; genetic model; in vitro st Autoimmune diabetes; Dendritic cells; H-2 congenic non-obese diabetic mice; Non-MHC non-obese diabetic genes
dc.titleIntrinsic in vitro abnormalities in dendritic cell generation caused by non-MHC non-obese diabetic genes
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume80
dc.date.issued2002
local.identifier.absfor060103 - Cell Development, Proliferation and Death
local.identifier.ariespublicationMigratedxPub24204
local.type.statusPublished Version
local.contributor.affiliationPrasad, S, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGoodnow, Christopher, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.startpage198
local.bibliographicCitation.lastpage206
local.identifier.doi10.1046/j.1440-1711.2002.01074.x
dc.date.updated2015-12-12T09:30:10Z
local.identifier.scopusID2-s2.0-0036215348
CollectionsANU Research Publications

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