Disease relevance of Th2 Cells

• Murine TH1 but not TH2 cells are recruited through P- and E-selectin into inflamed tissues, where they induce delayed-type hypersensitivity reactions [1].
• The activation of downstream signaling pathways of both T cell receptor (TCR) and interleukin 4 receptor (IL-4R) is essential for T helper type 2 (Th2) cell development, which is central to understanding immune responses against helminthic parasites and in allergic and autoimmune diseases [2].
• Myelin basic protein-specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from the disease [3].
• Elevated serum levels of soluble (s)CD30 have been found in some conditions in which a pathogenic role for Th2 cells has been suggested, such as atopy, Omenn's syndrome, systemic lupus erythematosus, as well as following infection with measles virus or human immuno-deficiency virus (HIV) [4].
• Because interferon alpha (IFN-alpha) is used in the therapy of the idiopathic hypereosinophilic syndrome, the effects of this cytokine on the survival of clonal Th2 cells isolated from the blood of 2 patients were determined [5].

High impact information on Th2 Cells

• Th2 cells produce cytokines (IL-4, IL-10 and IL-13) that are crucial for control of extracellular helminthic infections and promote atopic and allergic diseases [6].
• Activation of naive CD4(+) T-helper cells results in the development of at least two distinct effector populations, Th1 and Th2 cells [6].
• Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice [7].
• At higher doses, both Th1 and Th2 cells were deleted following their initial activation, whereas cells which secrete TGF-beta were resistant to deletion [8].
• Our results show that both types of TH cells induce the secretion of IgM and IgG3, whereas clones of TH1 and TH2 cells specifically induce antigen-specific B cells to secrete IgG2a and IgG1, respectively [9].

Chemical compound and disease context of Th2 Cells

• Allergen-specific Th2 cells accumulate at high frequencies in the skin of patients with atopic dermatitis (AD), where they contribute to the induction and maintenance of the lesions that are characteristic for the disease [10].
• Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophilia in a cell number-dependent manner [11].
• S1P and LPA induce the chemotaxis of Th1 and Th2 cells, an activity that is resistant to pertussis toxin (PTX) pretreatment in Th1, but is sensitive in Th2 cells [12].
• Chemoattractant receptor-homologous molecule expressed on Th2 cells activation in vivo increases blood leukocyte counts and its blockade abrogates 13,14-dihydro-15-keto-prostaglandin D2-induced eosinophilia in rats [13].
• A rapid flow cytometric assay to detect CD4+ and CD8+ T-helper (Th) 0, Th1 and Th2 cells in whole blood and its application to study cytokine levels in atopic dermatitis before and after cyclosporin therapy [14].

Biological context of Th2 Cells

• We show differential utilization of rafts in Th1 and Th2 cells by cholesterol depletion studies, which alters calcium signaling in Th1 but not Th2 cells [15].
• CD152 cross-linking together with stimulation of CD3 and CD28 on activated Th2 cells prevented activation-induced cell death (AICD) as a result of reduced Fas and FasL expression [16].
• In addition, CT and forskolin differentially influence the proto-oncogene mRNA expression in Th1 vs. Th2 cells after stimulation with Con A [17].
• LFA-1 overexpression was induced on cloned murine Th2 cells by transfection, resulting in autoreactivity [18].
• Among the possibilities are alterations to molecular mechanisms directly involved in the regulation of IL-4 gene expression or deficient regulatory activity of cytokines that antagonize Th2 cells [19].

Anatomical context of Th2 Cells

• Furthermore, Stat4-deficient lymphocytes demonstrate a propensity towards the development of Th2 cells [7].
• Immune responses dominated by interleukin-4 (IL-4)-producing T helper type 2 (TH2) cells or by interferon gamma (IFN-gamma)-producing T helper type 1 (TH1) cells express distinctive protection against infection with different pathogens [20].
• It is not known whether subsets of dendritic cells provide different cytokine microenvironments that determine the differentiation of either type-1 T helper (TH1) or TH2 cells [21].
• Here, we show that the expression of GADD45gamma is induced during T cell activation and that the level of expression is higher in TH1 cells than in TH2 cells [22].
• Here, we show that IL-6, probably secreted by antigen-presenting cells, is able to polarize naive CD4+ T cells to effector Th2 cells by inducing the initial production of IL-4 in CD4+ T cells [23].

Associations of Th2 Cells with chemical compounds

• These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy [24].
• These results suggest that pollen-derived E(1)-phytoprostanes not only resemble endogenous prostaglandin E(2) structurally but also functionally in that they act as regulators that modulate human DC function in a fashion that favors Th2 cell polarization [25].
• Paraformaldehyde fixation of the APCs following different conditions of activation indicated differential requirements for costimulatory signals by TH1 and TH2 cells [26].
• Functionally, CCL18 preferentially attracted in vitro-polarized Th2 cells and basophils, but not eosinophils and Th1 cells, and induced basophil histamine and intracellular calcium release [27].
• Th1 and, to a lesser extent, Th2 cells also stimulate the production of PGE2 by microglia [28].

Gene context of Th2 Cells

• Il4 and Il13, closely linked genes, are expressed monoallelically in TH2 cells [29].
• Stat6 is required for mediating responses to IL-4 and for development of Th2 cells [30].
• Inhibition of NF-kappa B activity prevented GATA-3 expression and TH2 cytokine production in developing, but not committed, TH2 cells [31].
• In response to IL-7 and IL-15, CXCR3(+) T(CM) and CCR4(+) T(CM) cells invariably generated fully differentiated CCR7(-) Th1 and Th2 cells, respectively, suggesting that they represent pre-Th1 and pre-Th2 cells [32].
• For example, although Th0, Th1, and Th2 cells are each found among blood CD4 T cells coordinately expressing CXCR3 and CCR4, Th1 but not Th2 cells can be CXCR3(+)CCR4(-), and Th2 but only rare Th1 cells are CCR4(+)CXCR3(-) [33].

Analytical, diagnostic and therapeutic context of Th2 Cells

• Studies of mice examined 3 d after adoptive transfer of differentiated T cell subsets revealed that Th1 but not Th2 cells were recruited to small intestine PP and LP [34].
• Flow cytometry analysis demonstrated that Pgp-1 expression increased when B cells were activated with supernatant of cloned Th2 cells, with LPS, or with IL-5, stimuli that induced polyclonal proliferation and differentiation [35].
• These results indicate that the better therapeutic efficacy of vaccination with C26/IL12 is associated with the production of C-binding Ab, an early infiltration of the metastatic lungs by activated T lymphocytes and a predominant systemic activation of Th1 more than Th2 cells [36].
• Signal transducer and activator of transcription (Stat)6 is a transcription factor important for the development of Th2 cells and regulation of gene expression by IL-4 and IL-13 [37].
• Interferon-gamma (IFN gamma), IL-4, and IL-10, the cytokines that discriminate between Th1 and Th2 cells and are involved in immunoregulation, were assayed by enzyme-linked immunosorbent assay [38].

References