Th2 cells differentiation

Basophils Drive Th2-Cell Differentiation through Secretion ofTh2 Cytokines and Antigen Presentation... 

GATA3 binding protein 3. GATA-3 expression inhibits the differentiation of Thl cells in vivo, induces Th2 cell differentiation, and increases functional capacity to secrete Th2 cytokines and enhance surface expression of markers for antigen-experienced Th2-committed cells. GATA-3 expression must be sustained to maintain the Th2 phenotype. 

IL-13 is a closely related cytokine to IL-4 that is also produced by Th2 cells. IL-13 along with IL-4 can switch B cells to produce IgE, however unlike IL-4, IL-13 cannot induce Th2 cell differentiation. In adults only 50% of asthma is associated with atopy, yet all forms of the disease are characterised by enhanced T-cell secretion of Th2 cytokines in the airways. Severe chronic asthma is characterised by the deposition of interstitial collagens in the lamina... 

NO has been reported to regulate both T-cell subsets equally, or preferentially induce Thl- but not Th2 cell differentiation. High concentrations of NO are regarded to be toxic and inhibit both Thl cell proliferation and IFN-y production. Thus low concentrations of NO seem to selectively induce Thl differentiation by up-regulating IL-12 receptor P2 expression (Niedbala et al. 2002). These studies have highlighted how different concentrations of NO can affect the outcome of immune reactions. 

A cytokine, secreted by TH2-cells, stimulates B-cells in different stages of their development. It may act as a growth factor or as a differentiation factor, causing B-lymphocytes to switch antibody to IgE. In T-cells it causes differentiation into TH2-cells. 

Fig. 3. Th2 cells provide cytokines such as IL-4, IL-5, IL-9 and IL-13, which are essential for differentiation, survival and activity of basophils, mast cells and eosinophils. IL-4 and IL-13 induce IgE production from B cells. IL-5 induces eosinophils, increases eosinophil survival and reduces apoptosis. IL-9 stimulates mast cells. 

B cells also have impact on T-cell differentiation. B-cell antigen presentation plays an important role at promoting Th2 responses and pathophysiology during allergic disorders. It has been shown that B-cell -/- mice and in mice selectively deficient in MHCII on B cells had decreased Th2 cytokines IL-4 and IL-5 [152]. Also in another study it has been reported that B-cell-derived exosomes can present allergen peptides and activate allergen-specific T cells to proliferate and produce Th2 cytokines IL-5 and IL-13 [42]. 

Intratracheal instillation 14d Alveolar macrophages activation production pro-inflammatory cytokines Blood high-levels pro-inflammatory cytokines differentiation of CD4+ T cell to Thl and Th2 cells [108]... 

Abishira-Amar, O., Gilbert, M., Jolly, M., Theze, J. andjankovic, D.I. (1992) IL-4 plays a dominant role in the differential development of ThO into Thl and Th2 cells. Journal of Immunology 148, 3820-3829. 

Campbell C, McSharry C. Alexander J, LiewFY CD44-CD254- regulatory T cells suppress differentiation and functions of Thl and Th2 cells, Leishmania major infection, and colitis in mice. J Immunol 2003 170 394-399. 

Stassen M, Jonuleit H, Muller C, Klein M, Richter C, Bopp T, Schmitt S, Schmitt E Differential regulatory capacity of CD25 4- T regulatory cells and preactivated CD25 4- T regulatory cells on development, functional activation, and proliferation of Th2 cells. J Immunol 2004 173 267-274. 

Fig. 4. Suppression of IgE production by NK1 cells is mediated by IFN-7.T0 investigate the mechanism of IgE inhibition by NK1 cells, in vitro differentiated NK1 cells were cocultured with purified B cells In the presence of neutralizing anti-IFN-7, anti-IE-4 and anti-IL-13 mAbs. a Inhibition of IgE and lgG4 by NK1 cells was significantly blocked by neutralization of IFN-7 ( p< 0.001 and p < 0.02, respectively). There was no influence in neutralization of IE-4 and IE-13 on NK1 cell-mediated IgE suppression, b Unlike Th2 cells, NK2 cells did not induce IgE in B cell cocultures [from 34, with permission].

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