Figure 3: CD4⁺ subsets and heterogeneity.

The classical view of CD4⁺ differentiation holds that naïve T cells differentiate into distinct subsets under the control of subset-specific environmental signals and downstream transcription factors. In this view, T helper 1 (Th1) cells express T-bet and produce interferon gamma (IFN-γ) whereas Th2 cells express Gata3 produce IL-4, IL-5, and IL-13. Th17 cells express RORγt and produce IL-17-family cytokines, Th9 cells express PU.1 and produce IL-9, and Th22 cells produce IL-22. Peripherally derived regulatory T cells promote immune tolerance, whereas T follicular helper (Tfh) cells are critical for B cell responses. In many cases subsets can by identified by the expression of specific cell surface markers; for example, CXCR3 marks Th1 cells while CCR6 marks Th17 cells. However, single cell technologies reveal that there is substantial overlap and heterogeneity between these different subsets in vivo.