Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
1999-12-10
pubmed:abstractText
There are two major mechanisms reported to prevent the autoreactivity of islet-specific CD8(+) T cells: ignorance and tolerance. When ignorance is operative, naïve autoreactive CD8(+) T cells ignore islet antigens and recirculate without causing damage, unless activated by an external stimulus. In the case of tolerance, CD8(+) T cells are deleted. Which factor(s) contributes to each particular outcome was previously unknown. Here, we demonstrate that the concentration of self antigen determines which mechanism operates. When ovalbumin (OVA) was expressed at a relatively low concentration in the pancreatic islets of transgenic mice, there was no detectable cross-presentation, and the CD8(+) T cell compartment remained ignorant of OVA. In mice expressing higher doses of OVA, cross-presentation was detectable and led to peripheral deletion of OVA-specific CD8(+) T cells. When cross-presentation was prevented by reconstituting the bone marrow compartment with cells incapable of presenting OVA, deletional tolerance was converted to ignorance. Thus, the immune system uses two strategies to avoid CD8(+) T cell-mediated autoimmunity: for high dose antigens, it deletes autoreactive T cells, whereas for lower dose antigens, it relies on ignorance.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-10097127, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-1348026, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-1901764, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-1901765, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-2455012, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-3543686, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-7650369, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-8176234, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-8539916, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-8939860, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-9064352, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-9221753, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-9670054, http://linkedlifedata.com/resource/pubmed/commentcorrection/10535986-9670055
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12703-7
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
CD8 T cell ignorance or tolerance to islet antigens depends on antigen dose.
pubmed:affiliation
Department of Nephrology, Medizinische Hochschule, Carl Neuberg Strasse 1, 30625 Hannover, Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't