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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2004-10-20
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pubmed:abstractText |
IL-2-deficient mice develop a lymphoproliferative and autoimmune disease characterized by autoimmune hemolytic anemia (AHA) and inflammatory bowel disease. We have previously reported that IL-2 is necessary for optimal up-regulation of CTLA-4, an inducible negative regulator of T cell activation. In this study, we have tested the hypothesis that reduced expression of CTLA-4 in IL-2-deficient T cells contributes to the pathogenesis of disease in IL-2-deficient mice. Expression of CTLA-4 as a transgene completely prevented lymphoaccumulation and AHA in IL-2-deficient mice. The normalization of T cell numbers was due to inhibition of expansion of conventional CD4+CD25- T cells rather than to rescue of the numbers or function of CD4+CD25+ regulatory T cells, suggesting that CTLA-4 expression on conventional T cells plays a role in maintaining normal T cell homeostasis. In addition, the inhibitory effect of the CTLA-4 transgene on T cell expansion was at least in part independent of CD28 expression. Our results suggest that deficient CTLA-4 expression on conventional T cells contributes to the pathophysiology of the lymphoproliferative disease and AHA in IL-2-deficient mice. Thus, restoring CTLA-4 expression in T cells may be an attractive strategy to control clinical autoimmune diseases in which CTLA-4 expression is reduced.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Ctla4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
173
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5415-24
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15494488-Anemia, Hemolytic, Autoimmune,
pubmed-meshheading:15494488-Animals,
pubmed-meshheading:15494488-Antigen-Presenting Cells,
pubmed-meshheading:15494488-Antigens, CD,
pubmed-meshheading:15494488-Antigens, CD28,
pubmed-meshheading:15494488-Antigens, Differentiation,
pubmed-meshheading:15494488-CD4-Positive T-Lymphocytes,
pubmed-meshheading:15494488-CTLA-4 Antigen,
pubmed-meshheading:15494488-Cell Death,
pubmed-meshheading:15494488-Gene Expression Regulation,
pubmed-meshheading:15494488-Growth Inhibitors,
pubmed-meshheading:15494488-Interleukin-2,
pubmed-meshheading:15494488-Lymphocyte Activation,
pubmed-meshheading:15494488-Lymphocyte Count,
pubmed-meshheading:15494488-Mice,
pubmed-meshheading:15494488-Mice, Knockout,
pubmed-meshheading:15494488-Mice, Transgenic,
pubmed-meshheading:15494488-Receptors, Interleukin-2,
pubmed-meshheading:15494488-Splenomegaly,
pubmed-meshheading:15494488-T-Lymphocyte Subsets,
pubmed-meshheading:15494488-Transgenes
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pubmed:year |
2004
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pubmed:articleTitle |
Transgenic expression of CTLA-4 controls lymphoproliferation in IL-2-deficient mice.
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pubmed:affiliation |
Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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