期刊
MOLECULAR IMMUNOLOGY
卷 46, 期 2, 页码 213-224出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2008.08.275
关键词
CD4+CD25+cells; PKC-theta; T cell development; Survival
资金
- American Cancer Society of Illinois Division
- Schweppe Foundation
- UIC Cancer center
- UIC IRB
- NIH [R01-AI053147]
CD4+CD25+ natural Treg cells, which are developed in the thymus, migrate to the periphery to actively maintain self-tolerance. Similar to conventional T cells, TCR signals are critical for the development and activation of Treg cell inhibitory function. While PKC-theta-mediated TCR signals are required for the activation of peripheral naive T cells, they are dispensable for their thymic development. Here, we show that mice deficient in PKC-theta had a greatly reduced number of CD4+Foxp3+ Treg cells, which was independent of PKC-theta-regulated survival, as transgenic Bcl-x(L) could not restore the Treg cell population in PKC-theta(-/-) mice. Active and WT PKC-theta markedly stimulated, whereas inactive PKC-theta and dominant negative NFAT inhibited Foxp3 promoter activity. In addition, mice-deficient in calcineurin A beta had a decreased Treg cell population, similar to that observed in PKC-theta deficient mice. It is likely that PKC-theta promoted the development of Treg cells by enhancing Foxp3 expression via activation of the calcineurin/NFAT pathway, Finally, Treg cells deficient in PKC-theta were as potent as WT Treg cells in inhibiting T cell activation, indicating that PKC-theta was not required for Treg cell-mediated inhibitory function. Our data highlight the contrasting roles PKC-theta plays in conventional T cell and natural Treg cell function. (c) 2008 Elsevier Ltd. All rights reserved.
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