Abstract

A number of distinguished populations with manifold functions and various pathways of differentiation have been identified within T lymphocytes. The cells expressing CD4 coreceptor on their cell surface are the most varied group. Depending on changes in different tissue microenvironments induced by such cytokines as IL-4, IFN-γ, IL-10 or TGF-β, CD4+ T lymphocytes can differentiate into alternative subpopulations performing helper, regulatory/suppressor function (Th1, Th2, Th9, Th17, Th22, Tfh, iTreg and Tr1). In the direction of lineage differentiation of these lymphocytes, transcription factors play the key role. The most important of them are T-bet, GATA3, RORγt, FOXP3, AHR and c-Maf. A cytokine binding to a specific receptor activates the transcription factors, other DNA-binding proteins, and epigenetic alterations, enabling the transcription of proper genetic information. The plasticity of CD4+ cell differentiation seems to be in dynamic balance between initial commitment and flexibility of these cells in the face of a changing environment. Even more, phenotypical and functional borders between particular subpopulations have turned out to be fluent. Then, the influence of extrinsic factors on the activation of mechanisms responsible for conversion of CD4+ T lymphocytes into functional mature cells appears to be more complicated than was previously thought.

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