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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 |
2003-10-21
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pubmed:abstractText |
Programmed death receptor 1 (PD-1) is expressed on thymocytes in addition to activated lymphocyte cells. Its ligation is thought to negatively regulate T cell activation, and PD-1(-/-) mice develop autoimmunity. To study the role of PD-1 on the development and function of a monoclonal CD8(+) T cell population, 2C TCR-transgenic/recombination-activating gene 2(-/-)/PD-1(-/-) mice were generated. Unexpectedly, approximately 30% of peripheral T cells in these mice were CD4/CD8 double negative (DN). Although the DN cells were not activated by Ag-expressing APCs, they functioned normally in response to anti-CD3/anti-CD28. These cells had a naive surface phenotype and lacked expression of NK1.1, B220, and gammadelta TCR; and the majority did not up-regulate CD8alphaalpha expression upon activation, arguing that they are not predominantly diverted gammadelta-lineage cells. The thymus was studied in detail to infer the mechanism of generation of DN peripheral T cells. Total thymus cellularity was reduced in 2C TCR-transgenic/recombination-activating gene 2(-/-)/PD-1(-/-) mice, and a relative increase in DN cells and decrease in double-positive (DP) cells were observed. Increased annexin V(+) cells among the DP population argued for augmented negative selection in PD-1(-/-) mice. In addition, an increased fraction of the DN thymocytes was HSA negative, suggesting that they had undergone positive selection. This possibility was supported by decreased emergence of DN PD-1(-/-) 2C cells in H-2(k) bone marrow chimera recipients. Our results are consistent with a model in which absence of PD-1 leads to greater negative selection of strongly interacting DP cells as well as increased emergence of DN alphabeta peripheral T cells.
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pubmed:grant |
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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,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Immune Sera,
http://linkedlifedata.com/resource/pubmed/chemical/Pdcd1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Programmed Cell Death 1 Receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Rag2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell...,
http://linkedlifedata.com/resource/pubmed/chemical/V(D)J recombination activating...
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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 |
171
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4574-81
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:14568931-Animals,
pubmed-meshheading:14568931-Antigens,
pubmed-meshheading:14568931-Antigens, CD28,
pubmed-meshheading:14568931-Antigens, CD3,
pubmed-meshheading:14568931-Antigens, CD4,
pubmed-meshheading:14568931-Antigens, Surface,
pubmed-meshheading:14568931-Apoptosis Regulatory Proteins,
pubmed-meshheading:14568931-CD8-Positive T-Lymphocytes,
pubmed-meshheading:14568931-Cell Differentiation,
pubmed-meshheading:14568931-Cell Division,
pubmed-meshheading:14568931-Cell Line, Tumor,
pubmed-meshheading:14568931-DNA-Binding Proteins,
pubmed-meshheading:14568931-Immune Sera,
pubmed-meshheading:14568931-Lymphocyte Activation,
pubmed-meshheading:14568931-Lymphocyte Count,
pubmed-meshheading:14568931-Mice,
pubmed-meshheading:14568931-Mice, Inbred C57BL,
pubmed-meshheading:14568931-Mice, Knockout,
pubmed-meshheading:14568931-Mice, Transgenic,
pubmed-meshheading:14568931-Programmed Cell Death 1 Receptor,
pubmed-meshheading:14568931-Receptors, Antigen, T-Cell, gamma-delta,
pubmed-meshheading:14568931-T-Lymphocyte Subsets,
pubmed-meshheading:14568931-Thymus Gland,
pubmed-meshheading:14568931-Up-Regulation
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pubmed:year |
2003
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pubmed:articleTitle |
Absence of programmed death receptor 1 alters thymic development and enhances generation of CD4/CD8 double-negative TCR-transgenic T cells.
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pubmed:affiliation |
Department of Pathology, 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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