Function of T Cells in the Immune System

CD4+ T helper cells

When one is exposed to a foreign pathogen, influenza virus for example, an antigen presenting cell (APC) such as a dendritic cell, will process and present viral antigens to your naïve CD4+ helper T cells.
The presentation of antigen serves to activate the T cell and stimulate it to secrete various cytokines and express specialized cell surface receptors. The specialized cell surface markers and cytokines will activate macrophages to destroy influenza, stimulate B cells to produce influenza specific antibodies, as well as maintain a steady level of self-tolerance to avoid destruction of your own cells and tissues.

CD4+ T cells signal and regulate an immune response to pathogens after interacting with an antigen-MHC (major histocompatibility) complex class II. MHC class II molecules are only expressed by a subset of immune cells called antigen-presenting cells. MHC class II recognition is essential for initiation of adaptive immune response, through signaling to lymphocytes such as the CD4+ helper T cell.

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CD4+ T cell sub types

The many roles just described are performed by a number of different subsets of CD4+T cells, described in the table below.

Naïve CD4+ T cells are activated by APCs to produce T helper (Th) cells, regulatory T cells (Tregs), and follicular helper T cells (TFH).
The Th cells can differentiate further to become Th1, Th2, Th9, Th17, or Th22 cells, depending upon the pathogen and types of cytokines present in the cellular microenvironment. They are responsible for responding to both intracellular as well as extracellular pathogens and have also been found to be involved in various diseases.

Tregs are responsible for maintaining self-tolerance so host cells remain safe from immune attack, while the follicular helper T cells (TFH) are responsible for helping B cells produce pathogen specific antibodies.

T Cells – An Orchestrated Motley Crew

The immune system is an intricate and fascinating network of many different cell types and signaling molecules that work together to protect the human body against foreign pathogens.

	Activation Cytokines	Phenotype	Cytokine Expression	Primary Function
Naive CD4+ T cell	Activated by APCs	CD45RA+ CCR7+	IL-2	Proliferation and differentiation into subsets
Th1 T helper type 1	IL-12 IFN-gamma	CXCR3+	IFN-gamma TNF-alpha and beta	Production of pro-inflammatory cytokines; cell-mediated immunity
Th2 T helper type 2	IL-4 IL-2	CRTH2+ CCR4+	IL-4, IL-5 IL-13, IL-15	Production of anti-inflammatory cytokines; promote allergic response; evoke strong antibody response
Th17 T helper type 17	TGF-beta, IL-6, IL-21, IL-23	CCR6+ CD161+	IL 17, IL-21 IL-22, IL-26	Respond to bacteria, fungi, and viruses; auto-immune diseasses
Th22 T helper type 22	IL-6	CCR4+ CCR10+	IL-22	Mucosal immune response; inflammatory disease; barriere defense
Th9 T helper type 9	TGF-beta IL-4	?	IL-9 IL-10	Humoral immunity through B cell interactions; functions on many cell types including mast cells and other CD4+ T cells
TFH Follicular helper T cells	IL-6 IL-21	CXCR5+ ICOS+	IL-4 IL-21	Antigen specific B cell immunity
nTreg Natural regulatory T cells	TGF-beta IL-2	CD25+ FOXP3+	TGF-beta IL-10	Maintenance of self-tolerance

CD8+ T cells

Naive CD8+ T cells drive the immune response by reacting to intracellular pathogens such as viruses with expansion and differentiation into cytotoxic effector cells. CD8+ T cells perform their cytotoxic function through the secretion of cytokines such as TNF-alpha and IFN-gamma or cytotoxic granules or through FasL/Fas interactions. During an infection, naive CD8+ T cells are primed by antigen-presenting cells (APCs) in secondary lymphoid organs such as lymph nodes (LN) and spleen. CD8+ T cells are MHC I-restricted; MHC class I molecules are expressed on the surface of all nucleated cells in an organism. MHC class I proteins function to present “self” intracellular antigens. When cells become infected by intracellular pathogens, such as viruses, MHC class I proteins bind and display protein fragments (antigen) of the target pathogen on the cell surface. This helps T cells and other components of the immune system to identify and coordinate that the cell is destroyed. Cytotoxic CD8+ T cells of the adaptive immune system are the most powerful effectors in the anticancer immune response and constitute the backbone of cancer immunotherapy.

CD8+ T cell subtype

Naïve CD8+ T cells can differentiate into effector or memory cell types. T cells activated to become effector cells differentiate into Tc1 or Tc2 cells. Tc1 cells can kill target cells directly or indirectly upon stimulation by cytokines such as IL-2 and IL-12. Additionally, cytotoxic Tc1 cells can release IFN-gamma or TNF-alpha for further modulation of immune responses. Tc2 T cells on the other hand modulate their function through the secretion of cytokines IL-4, IL-5, IL-10 and IL-13. In addition to these well-characterized subtypes, new subtypes such as Tc9, Tc17 and Tc22 have been identified, each activated by and producing different cytokines (see diagram).