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

Abstract

Naturally occurring CD4(+)CD25(+)Foxp3(+) T regulatory cells (nTregs) regulate lung allergic responses through production of IL-10 and TGF-β. nTregs from CD8(-/-) mice failed to suppress lung allergic responses and were characterized by reduced levels of Foxp3, IL-10, and TGF-β, 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.

• Authors: Anthony Joetham, Masakazu Okamoto, Katsuyuki Takeda, Michaela Schedel, Hiroshi Ohnishi, Azzeddine Dakhama, Erwin W Gelfand
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 186 Issue 1 Pg. 113-20 (Jan 01 2011) ISSN: 1550-6606 [Electronic] United States
• PMID: 21115736 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• CD8 Antigens
• CD8 antigen, alpha chain
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• Interleukin-6
• Receptors, Interleukin-6
• Transforming Growth Factor beta
• Interleukin-10

Topics

• Animals
• CD8 Antigens (genetics, physiology)
• Cells, Cultured
• Female
• Forkhead Transcription Factors (deficiency, genetics)
• Immunophenotyping
• Immunosuppression Therapy
• Interleukin-10 (antagonists & inhibitors)
• Interleukin-6 (biosynthesis, deficiency, genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Interleukin-6 (antagonists & inhibitors, physiology)
• Respiratory Hypersensitivity (genetics, immunology, metabolism)
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Transforming Growth Factor beta (antagonists & inhibitors)