T cells are immune cells, activated as an adaptive immune response to release cytokines that help innate and adaptive immunity. These cells do not bind to pathogen but bind to peptides generated by the degradation of these pathogens and presented on major histocompatibility (MHC) complex molecules, found in antigen presenting cells such as dendritic cells, B-cells, and macrophages. These T cells have receptors with alpha (light): beta (heavy) chain or in some rare cases, they have gamma: delta chain. These chains are synthesized in the thymus and are derived from the same precursor (Parham 79). There are two classes of MHC molecules, MHCI and II. The naïve T cells in the secondary lymphoid; when they encounter an antigen presented on MHC of dendritic cells, they differentiate and proliferate into effector T cells, CD8 or CD4 T cells depending on the class of MHC antigen complex the naïve T cell bind to. These effector T cells then are transported to the site of infection where they encounter target cells with specific antigen MHC complex. The target cells activate these effector CD8 (binds to MHCI) and CD4 (binds to MHCII antigen complex) into cytotoxic T cells and helper T cell 1 Th1.
CD4 T cell also differentiate into another subset along with Th1, called Th2 (helper T cell 2)which interacts with naive antigen presenting B cells in lymphoid body with the specificity of same antigen as themselves and help activate B cells which differentiate further into antibody producing plasma B cells. Th2 produces cytokines such as IL-4, IL5 and 13, which help in regulating humoral immunity and allergic reactions. Memory T cells are produced in the primary response during the colonial expansion of both short-lived pathogen specific T cell, which work to stop the infection and the long-lived memory T cells that will form future protection against pathogen (Parham 102). Memory T cells increase the speed of secondary response. A clear example of T cell coordinating adaptive immune response is the production of cytokines such as IFN gamma by Th1 cell to regulate adaptive immune response by recruiting inflammatory cells such as macrophages, and dendritic cells to the site of infection to engulf and kill phagocytes.
Th17 is one of the lineages of effector T cells. Unlike Th1 and Th2 cells Th17 expresses cytokines IL-17, 17F, 6, 21, 22, and TNF alpha, are known to regulate the accumulation of inflammatory cells at the site of infections and play a pathogenic role in autoimmunity (Romagnani, Maggi, Liotta, Cosmi, & Annunziato 7). Moreover, the differentiation pathway of Th17 is unique for it does not share any downstream transcription elements with Th1 and Th2. Th17 cells are found at the interfaces between the internal environment and external environment such as lining of intestine, skin and protect these surfaces from pathogenic bacteria. Th17 cells are stimulated by IL-23, which has a very similar subunit to IL-12 that is used to stimulate Th1 cell. Many of the surface marker of Th1 are also found in Th17; however, expression of certain markers such as markers from TNF super family, CD28 family, B7 family, and inducible co-stimulator are expressed more intensely in Th17 cells than Th1.
Evidence show that Th1 and Th2 become resistant to proliferation towards Th17 and its IL23 is stimulated by IL-17 cytokine. The early defining phase of Th17 differentiation from naïve CD4 cell is induced by an anti-inflammatory cytokine called TGF beta and IL-6. The presence of these cytokines plays a role in differentiation of Th17. TGF beta is also known to play a role in differentiation of T regulatory cells. Therefore, depending on the presence of IL-6, TGF beta either induces the differentiation of T reg. cell or Th17 from naïve CD4 T cells. The presence of TGF beta and IL-6 up-regulate the expression of IL 23 receptor on developing Th17 cells, which causes rapid proliferation of these cells after interacting with IL-23. This is known to play an important role in further survival, expansion, and programming of Th17 cells (Ivanov, & Lindén 280). TGF beta and IL-6 induce expression of orphan nuclear receptor RORgammat that is considered the main transcription factor of differentiation of Th17. Th17 cells regulate the recruitment of inflammatory cells such as neutrophils to the site of infection and attack the pathogen by secreting defence. This causes a degree of inflammation and removal of phagocyte from the site of infection. Because of its inflammatory effects, Th17 is also thought to act as an effector of autoimmune disorders such as ulcerative colitis.
The results from microarray analyses in this article showed a commensal species of non-culturable gram-positive bacteria. Segmented filamentous bacteria (SFB) in the small intestine induce the increase in concentration of Th17 cells. SFB is known to recruit intraepithelial lymphocytes to the intestine. The accumulation of Th17 cells, induced by the colonization of SFB in germ free cells also involved in the induction of acute-phase inflammation is released during acute phase inflammation (Ivaylo, Koji, Manel, Eoin, Tatsuichiro, Ulas, Dongguang, Goldfarb, Santee, Lynch, Takeshi, Akemi, Kikuji, Kiyoshi, Yoshinori, Honda, & Littman 489). This study also showed that colonization of SFB protected the cell from pathogens. An increased number of gene expressions of anti-microbe and inflammation proteins were also seen to correlate with the colonization of SFB. These findings show that SFB microbes play a role in maturation of adaptive immune response in mucosal intestine through the accumulation of Th17 cells. These findings are important because this information will open doors to do more research to find out the exact mechanism of how these commensal microorganisms influence host immune system. By understanding these commensal regulated pathways, researchers can manipulate these pathways to enhance the mucosal immune response and come up with better ways of treating autoimmune diseases. Moreover, by understanding how SFB induce Th17 and how Th17 cells accumulate inflammatory response, researchers can administer an antibody, which could effect the expression of IL-23 and IL 17 to regulate Th17 response and cause beneficial effects for patients with intestinal autoimmune disorder such as crohn’s disease.
Works Cited
Ivaylo, Ivanov, Koji, Atarashi, Nicolas, Manel, Eoin, Brodie, Tatsuichiro, Shima, Ulas, Karaoz, Dongguang, Wei, Katherine, Goldfarb, Clark, Santee, Susan, Lynch, Takeshi, Tanoue, Akemi, Imaoka, Kikuji, Itoh, Kiyoshi, Takeda, Yoshinori, Umesaki, Honda, & Littman, Dan. “Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria. Cell.” 139, 485–498, 2009. 2009 Elsevier Inc.
Ivanov, Stefan, & Lindén, Anders. “Th-17 cells in the lungs?” Expert Review of Respiratory Medicine. 2007, 1(2); 279-293
Parham, Peter. “The Immune System. Principles of Adaptive Immunity. Antigen Recognition By T lymphocytes. Development of T Lymphocytes. Properties and Function of effector Tcells. The body’s Defenses against Infection.” Third edition. Garland Science, 2009. 79-315.
Romagnani S, Maggi E, Liotta F, Cosmi L, Annunziato F. “Properties and origin of human Th17 Cells.” Mol Immunol. 2009, 47(1):3-7.