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MeSH Review

Th1 Cells

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Disease relevance of Th1 Cells


High impact information on Th1 Cells

  • It appears, however, that after immunization, the antigen-specific response is predominantly polarized toward a Th2-type response, with production of cytokines that can inhibit the activation of Th1 cells and of macrophages, and the production of proinflammatory cytokines [6].
  • By secreting interleukins, CD4 alpha/beta TH1 cells activate MP, converting them from a habitat to a potent effector cell; TH2-dependent activities seem to be of minor importance [7].
  • GATA-3 for Th2 and T-bet for Th1 cells expressing interleukin-4 or interferon-gamma, respectively, are prime candidates for key transcription factors of cytokine memory [8].
  • Role of T-bet in commitment of TH1 cells before IL-12-dependent selection [9].
  • The IFN-gamma-inducible signal transducing factor (STF-IFN gamma) was activated in murine TH2 but not in TH1 cell clones, because in the latter the second chain of the IFN-gamma receptor (accessory factor 1 or IFN-gamma R beta) was absent [10].

Chemical compound and disease context of Th1 Cells


Biological context of Th1 Cells

  • GATA-3 mediated strong enhancement of IL-4 promoter activity in Th1 cells when the promoter was embedded in the minilocus or linked to HSS and IE, demonstrating that GATA-3 acts through these elements to regulate IL-4 gene expression [15].
  • The IL-12-induced Th1 cell phenotype was stable and was not significantly affected when repeatedly stimulated in the presence of recombinant IL-4 [16].
  • T-helper 1 (Th1) cells are believed to be the major producer of the type 1 cytokine interferon-gamma (IFN-gamma) in cell-mediated immunity against intracellular infection [17].
  • Moreover, PGD(2) and 15d-PGJ(2) strongly reduce the secretion of the Th1 promoting cytokine IL-12 and affect the synthesis of chemokines involved in Th1 cell chemotaxis, particularly CXCL10 [18].
  • Varying the dose of anti-CD3 mAb, the kinetics of activation, and coengagement of CD3 and CD28 failed to increase tyrosine phosphorylation in Th2 cells to levels reached in Th1 cells [19].

Anatomical context of Th1 Cells


Associations of Th1 Cells with chemical compounds


Gene context of Th1 Cells

  • IL-4 and IFN-gamma are the signature cytokines of Th2 and Th1 cells, respectively [28].
  • These data show that immature and mature DCs induce different types of T cell responses: inflammatory Th1 cells are induced by mature DCs, and IL-10-producing T cell regulatory 1-like cells by immature DCs [29].
  • Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host [30].
  • It inhibits some cell functions, including T-helper (Th1) cell activity (i.e., interleukin 2 and interferon gamma production), and stimulates other functions such as a natural killer (NK) activity [31].
  • The levels of CD25 are significantly higher in developing Th2 cells than in developing Th1 cells during in vitro differentiation [32].

Analytical, diagnostic and therapeutic context of Th1 Cells


  1. Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Kaplan, M.H., Sun, Y.L., Hoey, T., Grusby, M.J. Nature (1996) [Pubmed]
  2. An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. Nicholson, L.B., Greer, J.M., Sobel, R.A., Lees, M.B., Kuchroo, V.K. Immunity (1995) [Pubmed]
  3. T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus production. Cohn, L., Homer, R.J., Niu, N., Bottomly, K. J. Exp. Med. (1999) [Pubmed]
  4. Signal transducer and activator of transcription 6 is essential in the induction of contact hypersensitivity. Yokozeki, H., Ghoreishi, M., Takagawa, S., Takayama, K., Satoh, T., Katayama, I., Takeda, K., Akira, S., Nishioka, K. J. Exp. Med. (2000) [Pubmed]
  5. Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin. Aktas, O., Waiczies, S., Smorodchenko, A., Dorr, J., Seeger, B., Prozorovski, T., Sallach, S., Endres, M., Brocke, S., Nitsch, R., Zipp, F. J. Exp. Med. (2003) [Pubmed]
  6. The design of vaccines against Helicobacter pylori and their development. Del Giudice, G., Covacci, A., Telford, J.L., Montecucco, C., Rappuoli, R. Annu. Rev. Immunol. (2001) [Pubmed]
  7. Immunity to intracellular bacteria. Kaufmann, S.H. Annu. Rev. Immunol. (1993) [Pubmed]
  8. Cytokine memory of T helper lymphocytes. Löhning, M., Richter, A., Radbruch, A. Adv. Immunol. (2002) [Pubmed]
  9. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Mullen, A.C., High, F.A., Hutchins, A.S., Lee, H.W., Villarino, A.V., Livingston, D.M., Kung, A.L., Cereb, N., Yao, T.P., Yang, S.Y., Reiner, S.L. Science (2001) [Pubmed]
  10. Lack of interferon gamma receptor beta chain and the prevention of interferon gamma signaling in TH1 cells. Pernis, A., Gupta, S., Gollob, K.J., Garfein, E., Coffman, R.L., Schindler, C., Rothman, P. Science (1995) [Pubmed]
  11. Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma. Huang, T.J., MacAry, P.A., Eynott, P., Moussavi, A., Daniel, K.C., Askenase, P.W., Kemeny, D.M., Chung, K.F. J. Immunol. (2001) [Pubmed]
  12. Immunological predictors of different responses to combination therapy with interferon alpha and ribavirin in patients with chronic hepatitis C. Amaraa, R., Mareckova, H., Urbanek, P., Fucikova, T. J. Gastroenterol. (2003) [Pubmed]
  13. Cyclophosphamide uncovers two separate macrophage subpopulations with opposite immunogenic potential and different patterns of monokine production. Marcinkiewicz, J., Bryniarski, K., Ptak, W. Cytokine (1994) [Pubmed]
  14. An HPLC method to determine tryptophan and kynurenine in serum simultaneously. Widner, B., Werner, E.R., Schennach, H., Fuchs, D. Adv. Exp. Med. Biol. (1999) [Pubmed]
  15. Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level. Lee, G.R., Fields, P.E., Flavell, R.A. Immunity (2001) [Pubmed]
  16. Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level. Sornasse, T., Larenas, P.V., Davis, K.A., de Vries, J.E., Yssel, H. J. Exp. Med. (1996) [Pubmed]
  17. Macrophages are a significant source of type 1 cytokines during mycobacterial infection. Wang, J., Wakeham, J., Harkness, R., Xing, Z. J. Clin. Invest. (1999) [Pubmed]
  18. Prostaglandin D2 affects the maturation of human monocyte-derived dendritic cells: consequence on the polarization of naive Th cells. Gosset, P., Bureau, F., Angeli, V., Pichavant, M., Faveeuw, C., Tonnel, A.B., Trottein, F. J. Immunol. (2003) [Pubmed]
  19. Early events of TCR signaling are distinct in human Th1 and Th2 cells. Hannier, S., Bitegye, C., Demotz, S. J. Immunol. (2002) [Pubmed]
  20. P-selectin glycoprotein ligand-1 (PSGL-1) on T helper 1 but not on T helper 2 cells binds to P-selectin and supports migration into inflamed skin. Borges, E., Tietz, W., Steegmaier, M., Moll, T., Hallmann, R., Hamann, A., Vestweber, D. J. Exp. Med. (1997) [Pubmed]
  21. Interleukin-12 primes human CD4 and CD8 T cell clones for high production of both interferon-gamma and interleukin-10. Gerosa, F., Paganin, C., Peritt, D., Paiola, F., Scupoli, M.T., Aste-Amezaga, M., Frank, I., Trinchieri, G. J. Exp. Med. (1996) [Pubmed]
  22. Selective expression of an interleukin-12 receptor component by human T helper 1 cells. Rogge, L., Barberis-Maino, L., Biffi, M., Passini, N., Presky, D.H., Gubler, U., Sinigaglia, F. J. Exp. Med. (1997) [Pubmed]
  23. Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction. Hessel, E.M., Chu, M., Lizcano, J.O., Chang, B., Herman, N., Kell, S.A., Wills-Karp, M., Coffman, R.L. J. Exp. Med. (2005) [Pubmed]
  24. IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508. Hwang, E.S., Hong, J.H., Glimcher, L.H. J. Exp. Med. (2005) [Pubmed]
  25. Upregulation of integrin alpha6/beta1 and chemokine receptor CCR1 by interleukin-12 promotes the migration of human type 1 helper T cells. Colantonio, L., Iellem, A., Clissi, B., Pardi, R., Rogge, L., Sinigaglia, F., D'Ambrosio, D. Blood (1999) [Pubmed]
  26. The hematopoiesis-specific GTP-binding protein RhoH is GTPase deficient and modulates activities of other Rho GTPases by an inhibitory function. Li, X., Bu, X., Lu, B., Avraham, H., Flavell, R.A., Lim, B. Mol. Cell. Biol. (2002) [Pubmed]
  27. A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells. Underhill, G.H., Zisoulis, D.G., Kolli, K.P., Ellies, L.G., Marth, J.D., Kansas, G.S. Blood (2005) [Pubmed]
  28. IFN-gamma represses IL-4 expression via IRF-1 and IRF-2. Elser, B., Lohoff, M., Kock, S., Giaisi, M., Kirchhoff, S., Krammer, P.H., Li-Weber, M. Immunity (2002) [Pubmed]
  29. Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. Jonuleit, H., Schmitt, E., Schuler, G., Knop, J., Enk, A.H. J. Exp. Med. (2000) [Pubmed]
  30. Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse. Sugimoto, T., Ishikawa, Y., Yoshimoto, T., Hayashi, N., Fujimoto, J., Nakanishi, K. J. Exp. Med. (2004) [Pubmed]
  31. Antimetastatic and antitumor activities of interleukin 10 in a murine model of breast cancer. Kundu, N., Beaty, T.L., Jackson, M.J., Fulton, A.M. J. Natl. Cancer Inst. (1996) [Pubmed]
  32. An IL-4-independent and CD25-mediated function of c-maf in promoting the production of Th2 cytokines. Hwang, E.S., White, I.A., Ho, I.C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  33. Expression of T-bet by CD4 T cells is essential for resistance to Salmonella infection. Ravindran, R., Foley, J., Stoklasek, T., Glimcher, L.H., McSorley, S.J. J. Immunol. (2005) [Pubmed]
  34. Activation-induced cell death limits effector function of CD4 tumor-specific T cells. Saff, R.R., Spanjaard, E.S., Hohlbaum, A.M., Marshak-Rothstein, A. J. Immunol. (2004) [Pubmed]
  35. Macrophage and T lymphocyte apoptosis during experimental pulmonary tuberculosis: their relationship to mycobacterial virulence. Ríos-Barrera, V.A., Campos-Peña, V., Aguilar-León, D., Lascurain, L.R., Meraz-Ríos, M.A., Moreno, J., Figueroa-Granados, V., Hernández-Pando, R. Eur. J. Immunol. (2006) [Pubmed]
  36. Modulation of experimental autoimmune encephalomyelitis: effect of altered peptide ligand on chemokine and chemokine receptor expression. Fischer, F.R., Santambrogio, L., Luo, Y., Berman, M.A., Hancock, W.W., Dorf, M.E. J. Neuroimmunol. (2000) [Pubmed]
  37. Reduction of Th1 cell activity in the peripheral circulation of patients with rheumatoid arthritis after treatment with a non-depleting humanized monoclonal antibody to CD4. Schulze-Koops, H., Davis, L.S., Haverty, T.P., Wacholtz, M.C., Lipsky, P.E. J. Rheumatol. (1998) [Pubmed]
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