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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2001-7-23
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pubmed:abstractText |
Thymectomy in mice on neonatal day 3 leads to the development of multiorgan autoimmune disease due to loss of a CD(+)CD25(+) T cell regulatory population in their peripheral lymphoid tissues. Here, we report the identification of a CD4(+) population of regulatory T cells in the circulation of humans expressing high levels of CD25 that exhibit in vitro characteristics identical with those of the CD4(+)CD25(+) regulatory cells isolated in mice. With TCR cross-linking, CD4(+)CD25(high) cells did not proliferate but instead totally inhibited proliferation and cytokine secretion by activated CD4(+)CD25(-) responder T cells in a contact-dependent manner. The CD4(+)CD25(high) regulatory T cells expressed high levels of CD45RO but not CD45RA, akin to the expression of CD45RB(low) on murine CD4(+)CD25(+) regulatory cells. Increasing the strength of signal by providing either costimulation with CD28 cross-linking or the addition of IL-2 to a maximal anti-CD3 stimulus resulted in a modest induction of proliferation and the loss of observable suppression in cocultures of CD4(+)CD25(high) regulatory cells and CD4(+)CD25(-) responder cells. Whereas higher ratios of CD4(+)CD25(high) T cells are required to suppress proliferation if the PD-L1 receptor is blocked, regulatory cell function is shown to persist in the absence of the PD-1/PD-L1 or CTLA-4/B7 pathway. Thus, regulatory CD4 T cells expressing high levels of the IL-2 receptor are present in humans, providing the opportunity to determine whether alterations of these populations of T cells are involved in the induction of human autoimmune disorders.
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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, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD274,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD45,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD80,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CD274 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ctla4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-DR Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/abatacept
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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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 |
167
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1245-53
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11466340-Antigens, CD,
pubmed-meshheading:11466340-Antigens, CD274,
pubmed-meshheading:11466340-Antigens, CD4,
pubmed-meshheading:11466340-Antigens, CD45,
pubmed-meshheading:11466340-Antigens, CD80,
pubmed-meshheading:11466340-Antigens, Differentiation,
pubmed-meshheading:11466340-Blood Proteins,
pubmed-meshheading:11466340-CD4-Positive T-Lymphocytes,
pubmed-meshheading:11466340-CTLA-4 Antigen,
pubmed-meshheading:11466340-Cells, Cultured,
pubmed-meshheading:11466340-Coculture Techniques,
pubmed-meshheading:11466340-HLA-DR Antigens,
pubmed-meshheading:11466340-Humans,
pubmed-meshheading:11466340-Immunoconjugates,
pubmed-meshheading:11466340-Immunosuppressive Agents,
pubmed-meshheading:11466340-Interleukin-2,
pubmed-meshheading:11466340-Kinetics,
pubmed-meshheading:11466340-Lymphocyte Activation,
pubmed-meshheading:11466340-Lymphocyte Count,
pubmed-meshheading:11466340-Membrane Glycoproteins,
pubmed-meshheading:11466340-Peptides,
pubmed-meshheading:11466340-RNA, Messenger,
pubmed-meshheading:11466340-Receptors, Antigen, T-Cell,
pubmed-meshheading:11466340-Receptors, Interleukin-2,
pubmed-meshheading:11466340-Signal Transduction,
pubmed-meshheading:11466340-T-Lymphocyte Subsets
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pubmed:year |
2001
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pubmed:articleTitle |
CD4+CD25high regulatory cells in human peripheral blood.
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pubmed:affiliation |
Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115. callan@rics.bwh.harvard.edu
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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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