T 세포 면역학

Helper T cells are essential regulators of adaptive immune responses and inflammatory diseases.

A sub-group of lymphocytes, helper T cells play an important role in establishing and maximizing the capabilities of the immune system. These cells are unusual in that they have little or no cytolytic or phagocytic activity. However, they are involved in activating and directing other immune cells.

After activation by professional antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells, antigen-specific CD4+ T cells differentiate into effector cells that are specialized in terms of the cytokines and effector molecules that they express on their membranes or secrete and their discrete effector functions.

Depending on the magnitude and patterns of TCR, costimulatory and cytokine signals received, T-helper cells differentiate into Th1, Th2, Th9, Th17, or Tfh cells, or other functional subsets including memory T cells. Differentiated Th cell subsets secrete different cytokines that have autocrine and paracrine functions to engage other leucocytes including macrophages, mast cells, eosinophils, neutrophils, natural killer (NK) cells, and B cells. Moreover, they can express different profiles of cell-surface molecules that determine their effector cell capacity. These include adhesion molecules and chemokine receptors that determine their capacity to home to and within lymphoid or peripheral tissues where offending target antigens may reside.

Multicolor flow cytometry is an excellent fit for determining the nature of these diverse cell populations. Since each T-helper subset has a characteristic cytokine signature that can be measured at the single-cell level, multicolor flow cytometry allows researchers to combine surface phenotyping and intracellular staining of cytokines and other signaling and effector molecules to analyze multiple parameters at once, and help speed investigation. Multiple soluble cytokines can also be quantitated in parallel using BD™ Cytometric Bead Array (CBA) technology in conjunction with a flow cytometer. Major Th-cell subsets include Th1, Th2, and Th17, and also recently discovered Th9 and Tfh.

More on T Helper Cell Products »

Th1 Cells

Th1 cells are involved in the cellular immune response and host defense against intracellular pathogens. These molecules are characterized by the production of pro-inflammatory cytokines like IFN-γ, IL-2, and lymphotoxin-α (LTα). Th1 cells are centrally involved in cell-mediated immunity. The cytokines produced by Th1 cells stimulate the phagocytosis and destruction of microbial pathogens by macrophages and other lymphocytes. Several chronic inflammatory diseases have been described as Th1-dominant diseases including multiple sclerosis, diabetes, and rheumatoid arthritis.

Th2 Cells

Th2 cells are involved in the humoral immune response and host defense against extracellular parasites. These cells are characterized by the production of IL-4, IL-5, IL-6, IL-10, and IL-13. Th2 cells are thought to play a role in allergic responses. Cytokines like IL-4 generally stimulate the production of antibodies directed toward large extracellular parasites, while IL-5 stimulates eosinophil response toward large extracellular parasites. Allergy and atrophy are thought to be Th2-dominant conditions. Th2 cells have historically been thought to be the source of IL-9. However, recent publications suggest the existence of a Th2-related cell type that is characterized by the secretion of IL-9 and IL-10. These so-called Th9 cells can differentiate from Th2 cells in the presence of TGF-β, or they can differentiate from a naïve CD4 cell with a combination of IL-4 and TGF-β. These cells may be involved in asthma and tissue inflammation.

Th1/Th2 Balance

When Th1 cells produce IFN-γ, this prompts macrophages to produce TNF and toxic forms of oxygen which destroy the microorganisms within the phagosomes and lysosomes. On the other hand, when Th2 cells produce IL-4 and IL-10, these cytokines block the microbial killing that is activated by IFN-γ. The Th1/Th2 relationship has also been investigated in regards to transplantation. Th1 responses have been implicated in most forms of acute graft or transplant rejection and graft-versus-host (GVHD) disease, while Th2 responses have been variably associated with either protection or chronic rejection. However, cloned Th1 or Th2 cells have a similar capacity to reject skin grafts in experimental models, and Tr1/Treg cells are now being implicated in protection and tolerance induction. The fetus is also analogous to an allograft, and Th2 or Treg responses are thought to be protective, while Th1 may lead to resorption or spontaneous abortion.

Th17 cells

Th17 cells

Th17 cells are involved in inflammation and host defense against extracellular pathogens. A subset of helper T cells that produce IL-17A, Th17 cells has been shown to play an important role in the induction of autoimmune tissue injury. They are distinct from Th1 or Th2 cells since they do not produce classical Th1 or Th2 cytokines such as IFN-γ or IL-4. They play a key role in mouse models of autoimmunity, and it has been suggested that the differentiation pathway from a naïve T-helper cell to a Th17 cell involves a combination of TGF-β and IL-6. RORγt is a key transcription factor involved in induction of Th17 cells. Some RORγt expression is induced in response to IL-6 or TGF-β, but the generation of Th17 cells requires TGF-β, as well as IL-6.

Furthermore, it is believed that the relative balance of IL-6 and TGF-β in steady state would tilt the balance in favor of either Th17 or Treg differentiation in diverse tissues. Induction of the Th17 subset requires TGF-β and IL-6, while amplification of IL-17A–producing cells is dependent upon TGF-β and IL-21. Maintenance of a Th17 response primarily depends on IL-23 (p19/p40). IL-23 binds to the IL-23 receptor that triggers downstream activation of STAT3 and subsequent upregulation of ROR-γ and production of IL-17A.

Since IL-17A leads to the induction of many proinflammatory factors such as TNF, IL-6, and IL-1β, it has been suggested that Th17 cells might be responsible for the development and/or progression of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and colitis.

Th17 cells