CD4 T Helper Cell Subsets and Related Human Immunological Disorders

Abstract

The immune system plays a critical role in protecting hosts from the invasion of organisms. CD4 T cells, as a key component of the immune system, are central in orchestrating adaptive immune responses. After decades of investigation, five major CD4 T helper cell (Th) subsets have been identified: Th1, Th2, Th17, Treg (T regulatory), and Tfh (follicular T helper) cells. Th1 cells, defined by the expression of lineage cytokine interferon (IFN)-γ and the master transcription factor T-bet, participate in type 1 immune responses to intracellular pathogens such as mycobacterial species and viruses; Th2 cells, defined by the expression of lineage cytokines interleukin (IL)-4/IL-5/IL-13 and the master transcription factor GAΤA3, participate in type 2 immune responses to larger extracellular pathogens such as helminths; Th17 cells, defined by the expression of lineage cytokines IL-17/IL-22 and the master transcription factor RORγt, participate in type 3 immune responses to extracellular pathogens including some bacteria and fungi; Tfh cells, by producing IL-21 and expressing Bcl6, help B cells produce corresponding antibodies; whereas Foxp3-expressing Treg cells, unlike Th1/Th2/Th17/Tfh exerting their effector functions, regulate immune responses to maintain immune cell homeostasis and prevent immunopathology. Interestingly, innate lymphoid cells (ILCs) have been found to mimic the functions of three major effector CD4 T helper subsets (Th1, Th2, and Th17) and thus can also be divided into three major subsets: ILC1s, ILC2s, and ILC3s. In this review, we will discuss the differentiation and functions of each CD4 T helper cell subset in the context of ILCs and human diseases associated with the dysregulation of these lymphocyte subsets particularly caused by monogenic mutations.

Tumour-directed microenvironment remodelling at a glance

“…Th1-specific transcription factors are STAT4 (Kaplan et al, 1996b) and T-bet (also known as TBX21) (Szabo et al, 2000), with hallmark cytokine IFN-γ (Ruterbusch et al, 2020). Th2-specific transcription factors are STAT6 (Kaplan et al, 1996a;Shimoda et al, 1996) and GATA3 (Zhang et al, 1997), and they release effector interleukins against pathogens (Zhu and Zhu, 2020). Th17 cells, characterised by high levels of IL-17, are closely related to Treg cells and are developmentally distinct from Th1 and Th2 cells (Maniati et al, 2010).…”

Chronic Immune Activation and CD4+ T Cell Lymphopenia in Healthy African Individuals: Perspectives for SARS-CoV-2 Vaccine Efficacy

“…CD4 + T cells play a pivotal role in the regulation of the immune system, protecting the host against various pathogens and autoimmunity (1). CD4 + T cells modulate the immune response by orchestrating responses of B-cells, CD8 + T cells and other components of the immune system.…”

“…CD4 + T cells modulate the immune response by orchestrating responses of B-cells, CD8 + T cells and other components of the immune system. To do so, CD4 + T cells, also designated as T-helper (TH) cells, branch into five major subsets: TH1, TH2, TH17, follicular T helper (TFH) and regulatory T cells (Treg) CD4 + T cells (1). These different subsets of TH cells are differentiated by the expression of different lineage markers and transcription factors as well as the production of different cytokines.…”

“…These different subsets of TH cells are differentiated by the expression of different lineage markers and transcription factors as well as the production of different cytokines. TH1 subsets express transcription factor T-bet, produce interferon (IFN)-g, and they exert effector function against intracellular microorganisms, such as mycobacteria and viruses; TH2 subsets express transcription factor GATA-3, produce the cytokines interleukin (IL)-4, IL-5, IL-6, IL-13, and they exert effector function against extracellular organisms, such as helminths; TH17 subsets express transcription factor RORgT, produce IL-17, as well as IL-22, and they exert effector function against intracellular organisms, such as bacteria and fungi; TFH CD4 + T cells express transcription factor Bcl6, produce IL-21 and their effector function is to help B-cells produce immunoglobulins; Tregs express FoxP3 transcription factor, produce the cytokines IL-10 and transformation growth factor (TGF)-b, and their effector functions include immune homeostasis (1). Tregs propitiate an adequate immune response by helping in the recruitment of T cells, facilitating the removal of pathogens and preventing excessive tissue damage; hence they are critical in the prevention of autoimmunity and other forms of immune dysregulation (2).…”

Beyond the Absence of CD4 T-Cell Count: A Novel Genetic CD4 T-Cell Deficiency Disorder With a Contingency Plan

“…In healthy individuals, the role of CD4 helper T (Th) cells is to protect the host from pathogens while preventing excessive inflammation to avoid collateral damage [ 1 ]. However, their action against invading pathogens, commensal microbes, or self-antigens can still be inappropriate, leading to chronic inflammation and autoimmunity [ 2 ]. CD4 T cells are key players in the immune response as they orchestrate CD8 cytotoxic T-cell responses and activate germinal centers, leading to B-cell activation and antibody production, while also exhibiting cytotoxic activity themselves.…”