CD4+ T helper 2 cells--microbial triggers, differentiation requirements and effector functions

Abstract

Over the past 10 years we have made great strides in our understanding of T helper cell differentiation, expansion and effector functions. Within the context of T helper type 2 (Th2) cell development, novel innate-like cells with the capacity to secrete large amounts of interleukin-5 (IL-5), IL-13 and IL-9 as well as IL-4-producing and antigen-processing basophils have (re)-emerged onto the type 2 scene. To what extent these new players influence αβ+ CD4+ Th2 cell differentiation is discussed throughout this appraisal of the current literature. We highlight the unique features of Th2 cell development, highlighting the three necessary signals, T-cell receptor ligation, co-stimulation and cytokine receptor ligation. Finally, putting these into context, microbial and allergenic properties that trigger Th2 cell differentiation and how these influence Th2 effector function are discussed and questioned.

Figure 1

T helper (Th) cell distinction. T helper cell differentiation of naive cells develops along a reversible continuum. Initial polarizing cytokines induce phosphorylation of signal transducer and activator of transcription (STAT) molecules and activation of lineage promoting transcription factors.

Figure 2

αβ⁺ CD4⁺ T helper type 2 (Th2) cell differentiation. A series of signals via the T-cell receptor, co-stimulatory receptors and cytokine receptors activate the appropriate transcription factors for il4 transcription and Th2 cell differentiation.