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Review
. 2009 Apr;46(1):1-6.
doi: 10.1016/j.cyto.2008.12.023. Epub 2009 Feb 23.

Signals for the execution of Th2 effector function

Deborah J Fowell  1
Affiliations
Review

Signals for the execution of Th2 effector function

Deborah J Fowell. Cytokine. 2009 Apr.

Abstract

Appropriate control of infection depends on the generation of lymphocytes armed with a particular array of cytokine and chemokine effector molecules. The differentiation of naïve T cells into functionally distinct effector subsets is regulated by signals from the T cell receptor (TCR) and cytokine receptors. Using gene knock-out approaches, the initiation of discrete effector programs appears differentially sensitive to the loss of individual TCR signaling components; likely due to differences in the transcription factors needed to activate individual cytokine genes. Less well understood however, are the signal requirements for the execution of effector function. With a focus on Th2 cells and the kinase ITK, we review recent observations that point to differences between the signals needed for the initiation and implementation of cytokine programs in CD4+ T cells. Indeed, Th2 effector cells signal differently from both their naïve counterparts and from Th1 effectors suggesting they may transduce activation signals differently or may be selectively receptive to different activation signals. Potential regulation points for effector function lie at the level of transcription and translation of cytokine genes. We also discuss how provision of these execution signals may be spatially segregated in vivo occurring at tissue sites of inflammation and subject to modulation by the pathogen itself.

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Figures

Figure 1
Figure 1
Signaling differences in Th1 and Th2 effectors.
Figure 2
Figure 2. Possible ITK-dependent control points in Th2 effector function
ITK is an amplifier of the TCR-dependent calcium flux and could modulate Th2 effector function at a number of levels including: 1) Activation of NFAT for increased cytokine transcription through binding to the IL-4 promoter and HSVA 3′ enhancer element; 2) Maintenance of GATA3 expression at the level of transcription or protein stability via ERK activation; 3) Translational enhancement via ERK; 4) Expression of AP1 and/or IL-4 mRNA stability via p38. CNS, conserved non-coding sequence; CIRE, conserved element in the first intron of the il4 gene; HS, DNase hypersensitivity site.
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