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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2000-11-21
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pubmed:abstractText |
TNF is a proinflammatory cytokine with opposing death/no-death effects in vivo and in vitro. Our studies showed that TNF regulates mouse thymocyte production, inducing both apoptosis and proliferation of the most immature CD3(-)CD4(-)CD8(-) triple negative (TN) subset within a broad range of dosages (10(1)-10(5) pg/ml) in the presence of IL-7. TNF apoptosis affected only the TN3 (CD44(-)CD25(+)) and TN4 (CD44(-)CD25(-)) subsets that expressed both TNFR-p55 and -p75. Although each TNFR alone could mediate TNF apoptosis, maximal apoptosis was seen in C57BL/6J wild type, which expressed both TNFRs. TNF also induced proliferation of TN3 cells at higher doses (10(4)-10(5) pg/ml) mediated only by TNFR-p75. Both anti-TNFR-p55 and -TNFR-p75 mAb inhibited apoptosis but only anti-p75 inhibited proliferation. TNF also regulated TN proliferation to IL-7 because TNFR knockout (KO), TNF KO, and TNF/lymphotoxin alpha and beta triple KO mice showed 2- to 3-fold increased responses not seen in C57BL/6J wild type. In vivo, TNFR KO mice showed thymic hypertrophy with a 60% increase in total thymocytes, with no effect on the CD4/CD8 subsets. We conclude that TNF maintains homeostatic control of total thymocyte production by negative selection of TN3 and TN4 prothymocytes and down-regulation of their proliferation to endogenous IL-7.
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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/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD44,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD8,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-7,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphotoxin-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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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 |
15
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pubmed:volume |
165
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5621-30
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11067918-Animals,
pubmed-meshheading:11067918-Antibodies, Monoclonal,
pubmed-meshheading:11067918-Antigens, CD,
pubmed-meshheading:11067918-Antigens, CD3,
pubmed-meshheading:11067918-Antigens, CD4,
pubmed-meshheading:11067918-Antigens, CD44,
pubmed-meshheading:11067918-Antigens, CD8,
pubmed-meshheading:11067918-Apoptosis,
pubmed-meshheading:11067918-Cell Cycle,
pubmed-meshheading:11067918-Cell Differentiation,
pubmed-meshheading:11067918-Cells, Cultured,
pubmed-meshheading:11067918-Dose-Response Relationship, Immunologic,
pubmed-meshheading:11067918-Female,
pubmed-meshheading:11067918-Hypertrophy,
pubmed-meshheading:11067918-Interleukin-7,
pubmed-meshheading:11067918-Kinetics,
pubmed-meshheading:11067918-Lymphocyte Activation,
pubmed-meshheading:11067918-Lymphotoxin-alpha,
pubmed-meshheading:11067918-Mice,
pubmed-meshheading:11067918-Mice, Inbred C3H,
pubmed-meshheading:11067918-Mice, Inbred C57BL,
pubmed-meshheading:11067918-Mice, Knockout,
pubmed-meshheading:11067918-Mice, Transgenic,
pubmed-meshheading:11067918-Receptors, Interleukin-2,
pubmed-meshheading:11067918-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:11067918-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:11067918-Receptors, Tumor Necrosis Factor, Type II,
pubmed-meshheading:11067918-T-Lymphocyte Subsets,
pubmed-meshheading:11067918-Thymus Gland,
pubmed-meshheading:11067918-Tumor Necrosis Factor-alpha
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pubmed:year |
2000
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pubmed:articleTitle |
TNF regulates thymocyte production by apoptosis and proliferation of the triple negative (CD3-CD4-CD8-) subset.
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pubmed:affiliation |
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. jmgonzal@aecom.yu.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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