Journal
JOURNAL OF IMMUNOLOGY
Volume 186, Issue 1, Pages 113-120Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1001663
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Funding
- National Institutes of Health [AI-77609, HL-36577, HL-61005]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL036577, R01HL061005] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI077609, R56AI077609] Funding Source: NIH RePORTER
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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. The Journal of Immunology, 2011, 186: 113-120.
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