Differential regulation of IL-4Ralpha expression by antigen versus cytokine stimulation characterizes Th2 progression in vivo.

IL-4 promotes Th2 differentiation and provides immunity to helminth infections but is also associated with allergy and asthma. This suggests that precise adjustment of IL-4 responsiveness is needed to correctly balance immune responses. The IL-4Ralpha chain is an essential component of the IL-4 receptor and signals via STAT6.

Cutting edge: T-bet and IL-27R are critical for in vivo IFN-gamma production by CD8 T cells during infection.

CD8+ T cells are a major source of IFN-gamma, a key effector cytokine in immune responses against many viruses and protozoa. Although the transcription factor T-bet is required for IFN-gamma expression in CD4+ T cells, it is reportedly dispensable in CD8+ T cells, where the transcription factor Eomesodermin is thought to be sufficient. The diverse functions of IFN-gamma are mediated through the IFN-gammaR and STAT1.

The functional heterogeneity of type 1 effector T cells in response to infection is related to the potential for IFN-gamma production.

The expression of IFN-gamma is a hallmark of Th1 cells and CD8(+) effector T cells and is the signature cytokine of type 1 responses. However, it is not known whether T cells are homogeneous in their capacity to produce IFN-gamma, whether this potential varies between tissues, and how it relates to the production of other effector molecules. In the present study we used bicistronic IFN-gamma-enhanced yellow fluorescent protein (IFN-gamma-eYFP) reporter mice (Yeti) and MHC class I tetramers to directly quantify IFN-gamma expression at the single cell level.