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CD8 regulates T regulatory cell production of IL-6 and maintains their suppressive phenotype in allergic lung disease.

Authors: Joetham, A  Okamoto, M  Takeda, K  Schedel, M  Ohnishi, H  Dakhama, A  Gelfand, EW 
Citation: Joetham A, etal., J Immunol. 2011 Jan 1;186(1):113-20. Epub 2010 Nov 29.
Pubmed: (View Article at PubMed) PMID:21115736
DOI: Full-text: DOI:10.4049/jimmunol.1001663

Naturally occurring CD4(+)CD25(+)Foxp3(+) T regulatory cells (nTregs) regulate lung allergic responses through production of IL-10 and TGF-beta. nTregs from CD8(-/-) mice failed to suppress lung allergic responses and were characterized by reduced levels of Foxp3, IL-10, and TGF-beta, and high levels of IL-6. Administration of anti-IL-6 or anti-IL-6R to wild-type recipients prior to transfer of CD8(-/-) nTregs restored suppression. nTregs from IL-6(-/-) mice were suppressive, but lost this capability if incubated with IL-6 prior to transfer. The importance of CD8 in regulating the production of IL-6 in nTregs was demonstrated by the loss of suppression and increases in IL-6 following transfer of nTregs from wild-type donors depleted of CD8(+) cells. Transfer of nTregs from CD8(-/-) donors reconstituted with CD8(+) T cells was suppressive, and accordingly, IL-6 levels were reduced. These data identify the critical role of CD8-T regulatory cell interactions in regulating the suppressive phenotype of nTregs through control of IL-6 production.


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CRRD Object Information
CRRD ID: 5128630
Created: 2011-03-14
Species: All species
Last Modified: 2011-03-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.