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J Virol. Aug 1994; 68(8): 5126–5132.
PMCID: PMC236456

Differential Th1 and Th2 cell responses in male and female BALB/c mice infected with coxsackievirus group B type 3.

Abstract

Male and female BALB/c mice differ dramatically in susceptibility to myocarditis subsequent to coxsackievirus B3 (CVB3) infection. CVB3 infection of male mice results in substantial inflammatory cell infiltration of the myocardium, and virus-immune lymphocytes from these animals give predominantly a Th1 cell phenotypic response, as determined by predominant immunoglobulin G2a isotypic antibody production and elevated numbers of gamma interferon and interleukin-2 (IL-2)-producing CD4+ T lymphocytes. Females infected with the same virus give predominantly a Th2 cell phenotypic response, as determined by preferential immunoglobulin G1 antibody isotypic responses and increased precursor frequencies of IL-4- and IL-5-producing CD4+ T cells. Treatment of females with testosterone or males with estradiol prior to infection alters subsequent Th subset differentiation, suggesting that the sex-associated hormones have either a direct or indirect effect on CD4+ lymphocyte responses in this model. Treatment of females with 0.1 mg of monoclonal antibody to IL-4 reduces precursor frequencies of IL-4-producing CD4+ T cells and increases frequencies of gamma interferon-producing cells. This treatment also enhances myocardial inflammation, indicating a correlation between Th1-like cell responses and pathogenicity in CVB3 infection. The Th2-like cell may regulate Th1 cell activation. Adoptive transfer of T lymphocytes from CVB3-infected female mice into male animals suppresses the development of myocarditis in the recipients. Treatment of the female donors with monoclonal antibodies to either CD3, CD4, or IL-4 molecules abrogates suppression.

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  • Araneo BA, Dowell T, Diegel M, Daynes RA. Dihydrotestosterone exerts a depressive influence on the production of interleukin-4 (IL-4), IL-5, and gamma-interferon, but not IL-2 by activated murine T cells. Blood. 1991 Aug 1;78(3):688–699. [PubMed]
  • Bhalla AK. Hormones and the immune response. Ann Rheum Dis. 1989 Jan;48(1):1–6. [PMC free article] [PubMed]
  • Bloom BR, Salgame P, Diamond B. Revisiting and revising suppressor T cells. Immunol Today. 1992 Apr;13(4):131–136. [PubMed]
  • Bogen SA, Fogelman I, Abbas AK. Analysis of IL-2, IL-4, and IFN-gamma-producing cells in situ during immune responses to protein antigens. J Immunol. 1993 May 15;150(10):4197–4205. [PubMed]
  • Dalton DK, Pitts-Meek S, Keshav S, Figari IS, Bradley A, Stewart TA. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science. 1993 Mar 19;259(5102):1739–1742. [PubMed]
  • Daynes RA, Araneo BA. Contrasting effects of glucocorticoids on the capacity of T cells to produce the growth factors interleukin 2 and interleukin 4. Eur J Immunol. 1989 Dec;19(12):2319–2325. [PubMed]
  • Else KJ, Hültner L, Grencis RK. Modulation of cytokine production and response phenotypes in murine trichuriasis. Parasite Immunol. 1992 Jul;14(4):441–449. [PubMed]
  • Esser C, Radbruch A. Immunoglobulin class switching: molecular and cellular analysis. Annu Rev Immunol. 1990;8:717–735. [PubMed]
  • Falcone V, Marelli P, Zolfino I, Campa M. BCG-activated NK cells regulate the antibody response to SRBC and restore immune reactivity to PPD in BCG-infected mice. Immunol Lett. 1993 Jun;36(3):295–299. [PubMed]
  • Fenoglio JJ, Jr, Ursell PC, Kellogg CF, Drusin RE, Weiss MB. Diagnosis and classification of myocarditis by endomyocardial biopsy. N Engl J Med. 1983 Jan 6;308(1):12–18. [PubMed]
  • Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. [PMC free article] [PubMed]
  • Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O'Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991 Dec 1;147(11):3815–3822. [PubMed]
  • Fitch FW, McKisic MD, Lancki DW, Gajewski TF. Differential regulation of murine T lymphocyte subsets. Annu Rev Immunol. 1993;11:29–48. [PubMed]
  • Gajewski TF, Schell SR, Nau G, Fitch FW. Regulation of T-cell activation: differences among T-cell subsets. Immunol Rev. 1989 Oct;111:79–110. [PubMed]
  • Good MF, Boyd AW, Nossal GJ. Analysis of true anti-hapten cytotoxic clones in limit dilution microcultures after correction for "anti-self" activity: precursor frequencies, Ly-2 and Thy-1 phenotype, specificity, and statistical methods. J Immunol. 1983 May;130(5):2046–2055. [PubMed]
  • Grossman CJ. Regulation of the immune system by sex steroids. Endocr Rev. 1984 Summer;5(3):435–455. [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]
  • Huber SA, Job LP, Auld KR. Influence of sex hormones on Coxsackie B-3 virus infection in Balb/c mice. Cell Immunol. 1982 Feb;67(1):173–179. [PubMed]
  • Huber SA, Job LP, Woodruff JF. Sex-related differences in the pattern of coxsackievirus B-3-induced immune spleen cell cytotoxicity against virus-infected myofibers. Infect Immun. 1981 Apr;32(1):68–73. [PMC free article] [PubMed]
  • Huber SA, Lodge PA. Coxsackievirus B-3 myocarditis in Balb/c mice. Evidence for autoimmunity to myocyte antigens. Am J Pathol. 1984 Jul;116(1):21–29. [PMC free article] [PubMed]
  • Job LP, Lyden DC, Huber SA. Demonstration of suppressor cells in coxsackievirus group B, type 3 infected female Balb/c mice which prevent myocarditis. Cell Immunol. 1986 Mar;98(1):104–113. [PubMed]
  • Kendall C, Ionescu-Matiu I, Dreesman GR. Utilization of the biotin/avidin system to amplify the sensitivity of the enzyme-linked immunosorbent assay (ELISA). J Immunol Methods. 1983 Feb 11;56(3):329–339. [PubMed]
  • Lerner A, Wilson FM, Reyes MP. Enteroviruses and the heart (with special emphasis on the probable role of coxsackieviruses, group B, types 1-5). II. Observations in humans. Mod Concepts Cardiovasc Dis. 1975 Mar;44(3):11–15. [PubMed]
  • Leslie K, Blay R, Haisch C, Lodge A, Weller A, Huber S. Clinical and experimental aspects of viral myocarditis. Clin Microbiol Rev. 1989 Apr;2(2):191–203. [PMC free article] [PubMed]
  • Lyden DC, Olszewski J, Feran M, Job LP, Huber SA. Coxsackievirus B-3-induced myocarditis. Effect of sex steroids on viremia and infectivity of cardiocytes. Am J Pathol. 1987 Mar;126(3):432–438. [PMC free article] [PubMed]
  • Morris L, Troutt AB, Handman E, Kelso A. Changes in the precursor frequencies of IL-4 and IFN-gamma secreting CD4+ cells correlate with resolution of lesions in murine cutaneous leishmaniasis. J Immunol. 1992 Oct 15;149(8):2715–2721. [PubMed]
  • Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. [PubMed]
  • Oswald IP, Gazzinelli RT, Sher A, James SL. IL-10 synergizes with IL-4 and transforming growth factor-beta to inhibit macrophage cytotoxic activity. J Immunol. 1992 Jun 1;148(11):3578–3582. [PubMed]
  • Paavonen T. Hormonal regulation of lymphocyte functions. Med Biol. 1987;65(5-6):229–240. [PubMed]
  • Pearce EJ, Caspar P, Grzych JM, Lewis FA, Sher A. Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med. 1991 Jan 1;173(1):159–166. [PMC free article] [PubMed]
  • Peterson JD, Karpus WJ, Clatch RJ, Miller SD. Split tolerance of Th1 and Th2 cells in tolerance to Theiler's murine encephalomyelitis virus. Eur J Immunol. 1993 Jan;23(1):46–55. [PubMed]
  • Reyes MP, Lerner AM. Coxsackievirus myocarditis--with special reference to acute and chronic effects. Prog Cardiovasc Dis. 1985 May-Jun;27(6):373–394. [PubMed]
  • Röcken M, Saurat JH, Hauser C. A common precursor for CD4+ T cells producing IL-2 or IL-4. J Immunol. 1992 Feb 15;148(4):1031–1036. [PubMed]
  • Romagnani S. Induction of TH1 and TH2 responses: a key role for the 'natural' immune response? Immunol Today. 1992 Oct;13(10):379–381. [PubMed]
  • Romani L, Mencacci A, Cenci E, Spaccapelo R, Mosci P, Puccetti P, Bistoni F. CD4+ subset expression in murine candidiasis. Th responses correlate directly with genetically determined susceptibility or vaccine-induced resistance. J Immunol. 1993 Feb 1;150(3):925–931. [PubMed]
  • Romani L, Mencacci A, Cenci E, Spaccapelo R, Schiaffella E, Tonnetti L, Puccetti P, Bistoni F. Natural killer cells do not play a dominant role in CD4+ subset differentiation in Candida albicans-infected mice. Infect Immun. 1993 Sep;61(9):3769–3774. [PMC free article] [PubMed]
  • Sarvetnick N, Fox HS. Interferon-gamma and the sexual dimorphism of autoimmunity. Mol Biol Med. 1990 Aug;7(4):323–331. [PubMed]
  • Scharton TM, Scott P. Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice. J Exp Med. 1993 Aug 1;178(2):567–577. [PMC free article] [PubMed]
  • Steinberg AD, Huston DP, Taurog JD, Cowdery JS, Ravecheé ES. The cellular and genetic basis of murine lupus. Immunol Rev. 1981;55:121–154. [PubMed]
  • Stevenson MM, Tam MF. Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice. Clin Exp Immunol. 1993 Apr;92(1):77–83. [PMC free article] [PubMed]
  • Street NE, Mosmann TR. Functional diversity of T lymphocytes due to secretion of different cytokine patterns. FASEB J. 1991 Feb;5(2):171–177. [PubMed]
  • Styrt B, Sugarman B. Estrogens and infection. Rev Infect Dis. 1991 Nov-Dec;13(6):1139–1150. [PubMed]
  • Thomas JM, Carver FM, Cunningham P, Olsen L, Thomas FT. Veto cells induce long-term kidney allograft tolerance in primates without chronic immunosuppression. Transplant Proc. 1991 Feb;23(1 Pt 1):11–13. [PubMed]
  • Torbett BE, Laxer JA, Glasebrook AL. Frequencies of T cells secreting IL-2 and/or IL-4 among unprimed CD4+ populations. Evidence that clones secreting IL-2 and IL-4 give rise to clones which secrete only IL-4. Immunol Lett. 1990 Jan;23(3):227–233. [PubMed]
  • Varkila K, Chatelain R, Leal LM, Coffman RL. Reconstitution of C.B-17 scid mice with BALB/c T cells initiates a T helper type-1 response and renders them capable of healing Leishmania major infection. Eur J Immunol. 1993 Jan;23(1):262–268. [PubMed]
  • Weaver CT, Hawrylowicz CM, Unanue ER. T helper cell subsets require the expression of distinct costimulatory signals by antigen-presenting cells. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8181–8185. [PMC free article] [PubMed]
  • Weller AH, Simpson K, Herzum M, Van Houten N, Huber SA. Coxsackievirus-B3-induced myocarditis: virus receptor antibodies modulate myocarditis. J Immunol. 1989 Sep 15;143(6):1843–1850. [PubMed]
  • Wong CY, Woodruff JJ, Woodruff JF. Generation of cytotoxic T lymphocytes during coxsackievirus B-3 infection. III. Role of sex. J Immunol. 1977 Aug;119(2):591–597. [PubMed]
  • Woodruff JF. Viral myocarditis. A review. Am J Pathol. 1980 Nov;101(2):425–484. [PMC free article] [PubMed]
  • Woodruff JF, Woodruff JJ. Involvement of T lymphocytes in the pathogenesis of coxsackie virus B3 heart disease. J Immunol. 1974 Dec;113(6):1726–1734. [PubMed]
  • Yamamoto M, Fujihashi K, Beagley KW, McGhee JR, Kiyono H. Cytokine synthesis by intestinal intraepithelial lymphocytes. Both gamma/delta T cell receptor-positive and alpha/beta T cell receptor-positive T cells in the G1 phase of cell cycle produce IFN-gamma and IL-5. J Immunol. 1993 Jan 1;150(1):106–114. [PubMed]

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