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J Exp Med. 1989 December 1; 170(6): 2081–2095.
PMCID: PMC2189521

Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones


A cytokine synthesis inhibitory factor (CSIF) is secreted by Th2 clones in response to Con A or antigen stimulation, but is absent in supernatants from Con A-induced Th1 clones. CSIF can inhibit the production of IL-2, IL-3, lymphotoxin (LT)/TNF, IFN-gamma, and granulocyte-macrophage CSF (GM-CSF) by Th1 cells responding to antigen and APC, but Th2 cytokine synthesis is not significantly affected. Transforming growth factor beta (TGF-beta) also inhibits IFN-gamma production, although less effectively than CSIF, whereas IL-2 and IL-4 partially antagonize the activity of CSIF. CSIF inhibition of cytokine synthesis is not complete, since early cytokine synthesis (before 8 h) is not significantly affected, whereas later synthesis is strongly inhibited. In the presence of CSIF, IFN-gamma mRNA levels are reduced slightly at 8, and strongly at 12 h after stimulation. Inhibition of cytokine expression by CSIF is not due to a general reduction in Th1 cell viability, since actin mRNA levels were not reduced, and proliferation of antigen-stimulated cells in response to IL-2, was unaffected. Biochemical characterization, mAbs, and recombinant or purified cytokines showed that CSIF is distinct from IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IFN-gamma, GM-CSF, TGF-beta, TNF, LT, and P40. The potential role of CSIF in crossregulation of Th1 and Th2 responses is discussed.

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Selected References

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  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed]
  • Cherwinski HM, Schumacher JH, Brown KD, Mosmann TR. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987 Nov 1;166(5):1229–1244. [PMC free article] [PubMed]
  • Brown KD, Zurawski SM, Mosmann TR, Zurawski G. A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes. J Immunol. 1989 Jan 15;142(2):679–687. [PubMed]
  • Kim J, Woods A, Becker-Dunn E, Bottomly K. Distinct functional phenotypes of cloned Ia-restricted helper T cells. J Exp Med. 1985 Jul 1;162(1):188–201. [PMC free article] [PubMed]
  • Cher DJ, Mosmann TR. Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. J Immunol. 1987 Jun 1;138(11):3688–3694. [PubMed]
  • Coffman RL, Seymour BW, Lebman DA, Hiraki DD, Christiansen JA, Shrader B, Cherwinski HM, Savelkoul HF, Finkelman FD, Bond MW, et al. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev. 1988 Feb;102:5–28. [PubMed]
  • Killar L, MacDonald G, West J, Woods A, Bottomly K. Cloned, Ia-restricted T cells that do not produce interleukin 4(IL 4)/B cell stimulatory factor 1(BSF-1) fail to help antigen-specific B cells. J Immunol. 1987 Mar 15;138(6):1674–1679. [PubMed]
  • Stevens TL, Bossie A, Sanders VM, Fernandez-Botran R, Coffman RL, Mosmann TR, Vitetta ES. Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature. 1988 Jul 21;334(6179):255–258. [PubMed]
  • Giedlin MA, Longenecker BM, Mosmann TR. Murine T-cell clones specific for chicken erythrocyte alloantigens. Cell Immunol. 1986 Feb;97(2):357–370. [PubMed]
  • Stout RD, Bottomly K. Antigen-specific activation of effector macrophages by IFN-gamma producing (TH1) T cell clones. Failure of IL-4-producing (TH2) T cell clones to activate effector function in macrophages. J Immunol. 1989 Feb 1;142(3):760–765. [PubMed]
  • Swain SL, McKenzie DT, Weinberg AD, Hancock W. Characterization of T helper 1 and 2 cell subsets in normal mice. Helper T cells responsible for IL-4 and IL-5 production are present as precursors that require priming before they develop into lymphokine-secreting cells. J Immunol. 1988 Nov 15;141(10):3445–3455. [PubMed]
  • Budd RC, Cerottini JC, MacDonald HR. Selectively increased production of interferon-gamma by subsets of Lyt-2+ and L3T4+ T cells identified by expression of Pgp-1. J Immunol. 1987 Jun 1;138(11):3583–3586. [PubMed]
  • Firestein GS, Roeder WD, Laxer JA, Townsend KS, Weaver CT, Hom JT, Linton J, Torbett BE, Glasebrook AL. A new murine CD4+ T cell subset with an unrestricted cytokine profile. J Immunol. 1989 Jul 15;143(2):518–525. [PubMed]
  • Parish CR. The relationship between humoral and cell-mediated immunity. Transplant Rev. 1972;13:35–66. [PubMed]
  • Katsura Y. Cell-mediated and humoral immune responses in mice. III. Dynamic balance between delayed-type hypersensitivity and antibody response. Immunology. 1977 Mar;32(3):227–235. [PubMed]
  • Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989 Jan 1;169(1):59–72. [PMC free article] [PubMed]
  • Fernandez-Botran R, Sanders VM, Mosmann TR, Vitetta ES. Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells. J Exp Med. 1988 Aug 1;168(2):543–558. [PMC free article] [PubMed]
  • Gajewski TF, Fitch FW. Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol. 1988 Jun 15;140(12):4245–4252. [PubMed]
  • Horowitz JB, Kaye J, Conrad PJ, Katz ME, Janeway CA., Jr Autocrine growth inhibition of a cloned line of helper T cells. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1886–1890. [PubMed]
  • Kaye J, Porcelli S, Tite J, Jones B, Janeway CA., Jr Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells. J Exp Med. 1983 Sep 1;158(3):836–856. [PMC free article] [PubMed]
  • Tony HP, Parker DC. Major histocompatibility complex-restricted, polyclonal B cell responses resulting from helper T cell recognition of antiimmunoglobulin presented by small B lymphocytes. J Exp Med. 1985 Jan 1;161(1):223–241. [PMC free article] [PubMed]
  • Nabel G, Greenberger JS, Sakakeeny MA, Cantor H. Multiple biologic activities of a cloned inducer T-cell population. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1157–1161. [PubMed]
  • Watson J. Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. J Exp Med. 1979 Dec 1;150(6):1510–1519. [PMC free article] [PubMed]
  • Espevik T, Nissen-Meyer J. A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. J Immunol Methods. 1986 Dec 4;95(1):99–105. [PubMed]
  • Schumacher JH, O'Garra A, Shrader B, van Kimmenade A, Bond MW, Mosmann TR, Coffman RL. The characterization of four monoclonal antibodies specific for mouse IL-5 and development of mouse and human IL-5 enzyme-linked immunosorbent. J Immunol. 1988 Sep 1;141(5):1576–1581. [PubMed]
  • Abrams JS, Pearce MK. Development of rat anti-mouse interleukin 3 monoclonal antibodies which neutralize bioactivity in vitro. J Immunol. 1988 Jan 1;140(1):131–137. [PubMed]
  • Ohara J, Paul WE. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. [PubMed]
  • Vink A, Coulie PG, Wauters P, Nordan RP, Van Snick J. B cell growth and differentiation activity of interleukin-HP1 and related murine plasmacytoma growth factors. Synergy with interleukin 1. Eur J Immunol. 1988 Apr;18(4):607–612. [PubMed]
  • Uyttenhove C, Simpson RJ, Van Snick J. Functional and structural characterization of P40, a mouse glycoprotein with T-cell growth factor activity. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6934–6938. [PubMed]
  • Bond MW, Shrader B, Mosmann TR, Coffman RL. A mouse T cell product that preferentially enhances IgA production. II. Physicochemical characterization. J Immunol. 1987 Dec 1;139(11):3691–3696. [PubMed]
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. [PubMed]
  • White BA, Bancroft FC. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem. 1982 Aug 10;257(15):8569–8572. [PubMed]
  • Leader DP, Gall I, Lehrach H. The structure of a cloned mouse gamma-actin processed pseudogene. Gene. 1985;36(3):369–374. [PubMed]
  • Webb DR, Mason K, Semenuk G, Aune TM, Pierce CW. Purification and analysis of isoforms of soluble immune response suppressor (SIRS). J Immunol. 1985 Nov;135(5):3238–3242. [PubMed]
  • Crowle AJ, Hu CC. Split tolerance affecting delayed hypersensitivity and induced in mice by pre-immunization with protein antigens in solution. Clin Exp Immunol. 1966 Jul;1(3):323–335. [PubMed]
  • Kelso A, MacDonald HR, Smith KA, Cerottini JC, Brunner KT. Interleukin 2 enhancement of lymphokine secretion by T lymphocytes: analysis of established clones and primary limiting dilution microcultures. J Immunol. 1984 Jun;132(6):2932–2938. [PubMed]
  • Espevik T, Figari IS, Shalaby MR, Lackides GA, Lewis GD, Shepard HM, Palladino MA., Jr Inhibition of cytokine production by cyclosporin A and transforming growth factor beta. J Exp Med. 1987 Aug 1;166(2):571–576. [PMC free article] [PubMed]

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