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Immunol Cell Biol. 2012 Apr;90(4):396-403. doi: 10.1038/icb.2011.50. Epub 2011 Jun 7.

CD4 T cells play important roles in maintaining IL-17-producing γδ T-cell subsets in naive animals.

Author information

1
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Abstract

A proportional balance between αβ and γδ T-cell subsets in the periphery is exceedingly well maintained by a homeostatic mechanism. However, a cellular mechanism underlying the regulation remains undefined. We recently reported that a subset of developing γδ T cells spontaneously acquires interleukin (IL)-17-producing capacity even within naive animals through a transforming growth factor (TGF)β1-dependent mechanism, thus considered 'innate' IL-17-producing cells. Here, we report that γδ T cells generated within αβ T cell (or CD4 T cell)-deficient environments displayed altered cytokine profiles; particularly, 'innate' IL-17 expression was significantly impaired compared with those in wild-type mice. Impaired IL-17 production in γδ T cells was directly related to CD4 T-cell deficiency, because depletion of CD4 T cells in wild-type mice diminished and adoptive CD4 T-cell transfer into T-cell receptor β-/- mice restored IL-17 expression in γδ T cells. CD4 T cell-mediated IL-17 expression required TGFβ1. Moreover, Th17 but not Th1 or Th2 effector CD4 T cells were highly efficient in enhancing γδ T-cell IL-17 expression. Taken together, our results highlight a novel CD4 T cell-dependent mechanism that shapes the generation of IL-17+ γδ T cells in naive settings.

Comment in

PMID:
21647171
PMCID:
PMC3170686
DOI:
10.1038/icb.2011.50
[Indexed for MEDLINE]
Free PMC Article

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