CD4⁺T cells: differentiation and functions

Abstract

CD4⁺T cells are crucial in achieving a regulated effective immune response to pathogens. Naive CD4⁺T cells are activated after interaction with antigen-MHC complex and differentiate into specific subtypes depending mainly on the cytokine milieu of the microenvironment. Besides the classical T-helper 1 and T-helper 2, other subsets have been identified, including T-helper 17, regulatory T cell, follicular helper T cell, and T-helper 9, each with a characteristic cytokine profile. For a particular phenotype to be differentiated, a set of cytokine signaling pathways coupled with activation of lineage-specific transcription factors and epigenetic modifications at appropriate genes are required. The effector functions of these cells are mediated by the cytokines secreted by the differentiated cells. This paper will focus on the cytokine-signaling and the network of transcription factors responsible for the differentiation of naive CD4⁺T cells.

Figure 1

Influence of distinct cytokine milieu in the differentiation of CD4⁺T cells. Blue arrows show the differentiation of naïve cells in the presence of particular cytokines. The green arrows represent the self-amplification phase by the encircled cytokines. Plasticity of T cell subset under the influence of specific cytokine is represented by the red arrows. Along with Th subset, the master regulator is shown. However, Bcl6 has not yet been identified as the master regulator, but it plays major role in the differentiation of Tfh.