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Nat Immunol. 2010 Sep;11(9):862-71. doi: 10.1038/ni.1917. Epub 2010 Aug 8.

Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells.

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  • 1Division of Immunology, Infection and Inflammatory Diseases, King's College London, Medical Research Council Centre for Transplantation, Guy's Hospital, London, UK.

Abstract

In this study we demonstrate a new form of immunoregulation: engagement on CD4(+) T cells of the complement regulator CD46 promoted the effector potential of T helper type 1 cells (T(H)1 cells), but as interleukin 2 (IL-2) accumulated, it switched cells toward a regulatory phenotype, attenuating IL-2 production via the transcriptional regulator ICER/CREM and upregulating IL-10 after interaction of the CD46 tail with the serine-threonine kinase SPAK. Activated CD4(+) T cells produced CD46 ligands, and blocking CD46 inhibited IL-10 production. Furthermore, CD4(+) T cells in rheumatoid arthritis failed to switch, consequently producing excessive interferon-gamma (IFN-gamma). Finally, gammadelta T cells, which rarely produce IL-10, expressed an alternative CD46 isoform and were unable to switch. Nonetheless, coengagement of T cell antigen receptor (TCR) gammadelta and CD46 suppressed effector cytokine production, establishing that CD46 uses distinct mechanisms to regulate different T cell subsets during an immune response.

PMID:
20694009
PMCID:
PMC4011020
DOI:
10.1038/ni.1917
[PubMed - indexed for MEDLINE]
Free PMC Article
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