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J Exp Med. 1993 July 1; 178(1): 349–353.
PMCID: PMC2191068

Chemically modified antigen preferentially elicits induction of Th1- like cytokine synthesis patterns in vivo


Differential activation of CD4+ T cell subsets in vivo leads to the development of qualitatively different effector responses. We identify an approach that allows selective activation of strongly Th1-dominated immune responses to protein antigens. Whereas in vivo administration of ovalbumin (OVA) induces cytokine synthesis that is neither Th1 nor Th2 dominated, administration of glutaraldehyde polymerized, high relative molecular weight OVA (OA-POL) leads to 20-fold increase in the ratio of interferon gamma (IFN-gamma)/IL-4 and IFN-gamma/IL-10 synthesis observed after short-term, antigen-mediated restimulation directly ex vivo. In contrast, concurrent in vivo administration of anti-IFN-gamma mAb and OVA or OA-POL results in marked increases in IL-4 and IL-10, and decreased IFN-gamma production, reflecting a polarization of the response towards a Th2-like pattern of cytokine synthesis. These observations may be useful in clinical settings including hypersensitivity, autoimmune diseases, and vaccine development where the ability to actively select specific patterns of cytokine gene expression would be advantageous.

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Selected References

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  • Finkelman FD, Holmes J, Katona IM, Urban JF, Jr, Beckmann MP, Park LS, Schooley KA, Coffman RL, Mosmann TR, Paul WE. Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol. 1990;8:303–333. [PubMed]
  • Salgame P, Abrams JS, Clayberger C, Goldstein H, Convit J, Modlin RL, Bloom BR. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science. 1991 Oct 11;254(5029):279–282. [PubMed]
  • Mosmann TR, Schumacher JH, Street NF, Budd R, O'Garra A, Fong TA, Bond MW, Moore KW, Sher A, Fiorentino DF. Diversity of cytokine synthesis and function of mouse CD4+ T cells. Immunol Rev. 1991 Oct;123:209–229. [PubMed]
  • Sher A, Gazzinelli RT, Oswald IP, Clerici M, Kullberg M, Pearce EJ, Berzofsky JA, Mosmann TR, James SL, Morse HC., 3rd Role of T-cell derived cytokines in the downregulation of immune responses in parasitic and retroviral infection. Immunol Rev. 1992 Jun;127:183–204. [PubMed]
  • Bretscher PA, Wei G, Menon JN, Bielefeldt-Ohmann H. Establishment of stable, cell-mediated immunity that makes "susceptible" mice resistant to Leishmania major. Science. 1992 Jul 24;257(5069):539–542. [PubMed]
  • Kapsenberg ML, Wierenga EA, Bos JD, Jansen HM. Functional subsets of allergen-reactive human CD4+ T cells. Immunol Today. 1991 Nov;12(11):392–395. [PubMed]
  • De Wit D, Van Mechelen M, Zanin C, Doutrelepont JM, Velu T, Gérard C, Abramowicz D, Scheerlinck JP, De Baetselier P, Urbain J, et al. Preferential activation of Th2 cells in chronic graft-versus-host reaction. J Immunol. 1993 Jan 15;150(2):361–366. [PubMed]
  • HayGlass KT, Stefura BP. Anti-interferon gamma treatment blocks the ability of glutaraldehyde-polymerized allergens to inhibit specific IgE responses. J Exp Med. 1991 Feb 1;173(2):279–285. [PMC free article] [PubMed]
  • Patterson R, Suszko IM, McIntire FC. Polymerized ragweed antigen E. I. Preparation and immunologic studies. J Immunol. 1973 May;110(5):1402–1412. [PubMed]
  • Johansson SG, Miller AC, Mullan N, Overell BG, Tees EC, Wheeler A. Glutaraldehyde-pollen-tyrosine: clinical and immunological studies. Clin Allergy. 1974 Sep;4(3):255–263. [PubMed]
  • Attallah NA, Kuroume T, Sehon AH. Conversion of nonimmunogenic low molecular weight ragweed components to immunogens for induction of homocytotropic antibody. Immunochemistry. 1975 Jul;12(6-7):555–559. [PubMed]
  • Hayglass KT, Gieni RS, Stefura WP. Long-lived reciprocal regulation of antigen-specific IgE and IgG2a responses in mice treated with glutaraldehyde-polymerized ovalbumin. Immunology. 1991 Aug;73(4):407–414. [PubMed]
  • Hayglass KT, Stefura WP. Antigen-specific inhibition of ongoing murine IgE responses. II. Inhibition of IgE responses induced by treatment with glutaraldehyde-modified allergens is paralleled by reciprocal increases in IgG2a synthesis. J Immunol. 1991 Oct 15;147(8):2455–2460. [PubMed]
  • Swain SL, Weinberg AD, English M, Huston G. IL-4 directs the development of Th2-like helper effectors. J Immunol. 1990 Dec 1;145(11):3796–3806. [PubMed]
  • Le Gros G, Ben-Sasson SZ, Seder R, Finkelman FD, Paul WE. Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med. 1990 Sep 1;172(3):921–929. [PMC free article] [PubMed]
  • Hoffmann B, Paul D. Precocious induction of tyrosine aminotransferase mRNA by hydrocortisone in cultured fetal rat hepatocytes at different developmental stages. J Cell Physiol. 1990 May;143(2):352–356. [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]
  • Chatelain R, Varkila K, Coffman RL. IL-4 induces a Th2 response in Leishmania major-infected mice. J Immunol. 1992 Feb 15;148(4):1182–1187. [PubMed]
  • Liew FY, Millott SM, Schmidt JA. A repetitive peptide of Leishmania can activate T helper type 2 cells and enhance disease progression. J Exp Med. 1990 Nov 1;172(5):1359–1365. [PMC free article] [PubMed]
  • Jardim A, Alexander J, Teh HS, Ou D, Olafson RW. Immunoprotective Leishmania major synthetic T cell epitopes. J Exp Med. 1990 Aug 1;172(2):645–648. [PMC free article] [PubMed]
  • Burstein HJ, Shea CM, Abbas AK. Aqueous antigens induce in vivo tolerance selectively in IL-2- and IFN-gamma-producing (Th1) cells. J Immunol. 1992 Jun 15;148(12):3687–3691. [PubMed]
  • Gajewski TF, Pinnas M, Wong T, Fitch FW. Murine Th1 and Th2 clones proliferate optimally in response to distinct antigen-presenting cell populations. J Immunol. 1991 Mar 15;146(6):1750–1758. [PubMed]

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