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. 1991 Mar;59(3):836–842. doi: 10.1128/iai.59.3.836-842.1991

In vivo effects of anticytokine antibodies on isotype restriction in Mesocestoides corti-infected BALB/c mice.

D M Estes 1, J M Teale 1
PMCID: PMC258335  PMID: 1997434

Abstract

Chronic infection of mice with the cestode Mesocestoides corti results in an antibody response restricted to immunoglobulins M (IgM) and G1 (IgG1). To determine which of the known lymphokines are involved in the restricted isotype response, we treated M. corti-infected mice with a panel of anticytokine monoclonal antibodies against interleukin-4 (IL-4), IL-5, IL-6, and gamma interferon. The effects of anti-IL-4 were of particular importance, since IL-4 is known to enhance IgG1 production and an IgG1 response predominates in infected animals. Interestingly, injection of anti-IL-4 alone had no effect on IgG1 levels at day 7 postinfection and actually enhanced levels at day 10. Decreases in IgM levels were observed in anti-IL-4-treated mice. Administration of anti-IL-5 inhibited IgM production early in infection, but no effects on IgG1 levels were observed. Treatment of infected mice with anti-gamma interferon had no effect on any of the isotypes analyzed. Treatment of infected mice with anti-IL-6 antibody had the most dramatic effects, with inhibition of IgM and IgG1 by day 14 of infection. The transient expression of IgG3, which is sometimes observed very early in the infection process, was also inhibited by anti-IL-6, suggesting that the inhibition observed was not isotype specific. To determine whether cytokines were acting in concert to effect the high IgM and IgG1 levels in infected animals, anticytokine antibodies were also injected in combinations. However, the only combinations that inhibited IgG1 levels contained anti-IL-6, and the extent of inhibition was not greater than that of anti-IL-6 alone. Results are discussed in terms of the effects of cytokines on parasite-induced isotype expression and the potential for IL-4-independent mechanisms of IgG1 production.

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Selected References

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  1. Abraham K. M., Teale J. M. Isotype restriction during infection of mice with the cestode Mesocestoides corti: role of immune suppression. J Immunol. 1987 Mar 15;138(6):1699–1704. [PubMed] [Google Scholar]
  2. Abraham K. M., Teale J. M. The contribution of parasite-specific T cells to isotype restriction in Mesocestoides corti-infected mice. J Immunol. 1987 Oct 15;139(8):2530–2537. [PubMed] [Google Scholar]
  3. Akerström B., Björck L. A physicochemical study of protein G, a molecule with unique immunoglobulin G-binding properties. J Biol Chem. 1986 Aug 5;261(22):10240–10247. [PubMed] [Google Scholar]
  4. Asano Y., Nakayama T., Kubo M., Fujisawa I., Karasuyama H., Singer A., Hodes R. J., Tada T. Analysis of two distinct B cell activation pathways mediated by a monoclonal T helper cell. II. T helper cell secretion of interleukin 4 selectively inhibits antigen-specific B cell activation by cognate, but not noncognate, interactions with T cells. J Immunol. 1988 Jan 15;140(2):419–426. [PubMed] [Google Scholar]
  5. Beagley K. W., Eldridge J. H., Kiyono H., Everson M. P., Koopman W. J., Honjo T., McGhee J. R. Recombinant murine IL-5 induces high rate IgA synthesis in cycling IgA-positive Peyer's patch B cells. J Immunol. 1988 Sep 15;141(6):2035–2042. [PubMed] [Google Scholar]
  6. Berton M. T., Uhr J. W., Vitetta E. S. Synthesis of germ-line gamma 1 immunoglobulin heavy-chain transcripts in resting B cells: induction by interleukin 4 and inhibition by interferon gamma. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2829–2833. doi: 10.1073/pnas.86.8.2829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bottomly K. A functional dichotomy in CD4+ T lymphocytes. Immunol Today. 1988 Sep;9(9):268–274. doi: 10.1016/0167-5699(88)91308-4. [DOI] [PubMed] [Google Scholar]
  8. Coffman R. L., Lebman D. A., Shrader B. Transforming growth factor beta specifically enhances IgA production by lipopolysaccharide-stimulated murine B lymphocytes. J Exp Med. 1989 Sep 1;170(3):1039–1044. doi: 10.1084/jem.170.3.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Coffman R. L., Ohara J., Bond M. W., Carty J., Zlotnik A., Paul W. E. B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells. J Immunol. 1986 Jun 15;136(12):4538–4541. [PubMed] [Google Scholar]
  10. Coffman R. L., Seymour B. W., Hudak S., Jackson J., Rennick D. Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science. 1989 Jul 21;245(4915):308–310. doi: 10.1126/science.2787531. [DOI] [PubMed] [Google Scholar]
  11. Coffman R. L., Seymour B. W., Lebman D. A., Hiraki D. D., Christiansen J. A., Shrader B., Cherwinski H. M., Savelkoul H. F., Finkelman F. D., Bond M. W. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev. 1988 Feb;102:5–28. doi: 10.1111/j.1600-065x.1988.tb00739.x. [DOI] [PubMed] [Google Scholar]
  12. Coffman R. L., Shrader B., Carty J., Mosmann T. R., Bond M. W. A mouse T cell product that preferentially enhances IgA production. I. Biologic characterization. J Immunol. 1987 Dec 1;139(11):3685–3690. [PubMed] [Google Scholar]
  13. Desai B. B., Abraham K. M., Teale J. M. The isotype potential of B cells present in BALB/c mice chronically infected with Mesocestoides corti. Cell Immunol. 1990 Oct 1;130(1):139–149. doi: 10.1016/0008-8749(90)90168-q. [DOI] [PubMed] [Google Scholar]
  14. Esser C., Radbruch A. Rapid induction of transcription of unrearranged S gamma 1 switch regions in activated murine B cells by interleukin 4. EMBO J. 1989 Feb;8(2):483–488. doi: 10.1002/j.1460-2075.1989.tb03401.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Finkelman F. D., Holmes J., Katona I. M., Urban J. F., Jr, Beckmann M. P., Park L. S., Schooley K. A., Coffman R. L., Mosmann T. R., Paul W. E. Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol. 1990;8:303–333. doi: 10.1146/annurev.iy.08.040190.001511. [DOI] [PubMed] [Google Scholar]
  16. Finkelman F. D., Katona I. M., Mosmann T. R., Coffman R. L. IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol. 1988 Feb 15;140(4):1022–1027. [PubMed] [Google Scholar]
  17. Finkelman F. D., Katona I. M., Urban J. F., Jr, Holmes J., Ohara J., Tung A. S., Sample J. V., Paul W. E. IL-4 is required to generate and sustain in vivo IgE responses. J Immunol. 1988 Oct 1;141(7):2335–2341. [PubMed] [Google Scholar]
  18. Harada N., Kikuchi Y., Tominaga A., Takaki S., Takatsu K. BCGFII activity on activated B cells of a purified murine T cell-replacing factor (TRF) from a T cell hybridoma (B151K12). J Immunol. 1985 Jun;134(6):3944–3951. [PubMed] [Google Scholar]
  19. Heinzel F. P., Sadick M. D., Holaday B. J., Coffman R. L., Locksley R. M. 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. doi: 10.1084/jem.169.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Isakson P. C., Puré E., Vitetta E. S., Krammer P. H. T cell-derived B cell differentiation factor(s). Effect on the isotype switch of murine B cells. J Exp Med. 1982 Mar 1;155(3):734–748. doi: 10.1084/jem.155.3.734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Johnson G. R., Nicholas W. L., Metcalf D., McKenzie I. F., Mitchell G. F. Peritoneal cell population of mice infected with Mesocestoides corti as a source of eosinophils. Int Arch Allergy Appl Immunol. 1979;59(3):315–322. doi: 10.1159/000232275. [DOI] [PubMed] [Google Scholar]
  22. Kinashi T., Harada N., Severinson E., Tanabe T., Sideras P., Konishi M., Azuma C., Tominaga A., Bergstedt-Lindqvist S., Takahashi M. Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II. Nature. 1986 Nov 6;324(6092):70–73. doi: 10.1038/324070a0. [DOI] [PubMed] [Google Scholar]
  23. Liu F. T., Bohn J. W., Ferry E. L., Yamamoto H., Molinaro C. A., Sherman L. A., Klinman N. R., Katz D. H. Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. J Immunol. 1980 Jun;124(6):2728–2737. [PubMed] [Google Scholar]
  24. Matsui K., Nakanishi K., Cohen D. I., Hada T., Furuyama J., Hamaoka T., Higashino K. B cell response pathways regulated by IL-5 and IL-2. Secretory microH chain-mRNA and J chain mRNA expression are separately controlled events. J Immunol. 1989 Apr 15;142(8):2918–2923. [PubMed] [Google Scholar]
  25. Mitchell G. F., Marchalonis J. J., Smith P. M., Nicholas W. L., Warner N. L. Studies on immune responses to larval cestodes in mice. Immunoglobulins associated with the larvae of Mesocestoides corti. Aust J Exp Biol Med Sci. 1977 Apr;55(2):187–211. doi: 10.1038/icb.1977.14. [DOI] [PubMed] [Google Scholar]
  26. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. 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] [Google Scholar]
  27. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  28. Muraguchi A., Hirano T., Tang B., Matsuda T., Horii Y., Nakajima K., Kishimoto T. The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med. 1988 Feb 1;167(2):332–344. doi: 10.1084/jem.167.2.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Murray P. D., McKenzie D. T., Swain S. L., Kagnoff M. F. Interleukin 5 and interleukin 4 produced by Peyer's patch T cells selectively enhance immunoglobulin A expression. J Immunol. 1987 Oct 15;139(8):2669–2674. [PubMed] [Google Scholar]
  30. Poo W. J., Conrad L., Janeway C. A., Jr Receptor-directed focusing of lymphokine release by helper T cells. Nature. 1988 Mar 24;332(6162):378–380. doi: 10.1038/332378a0. [DOI] [PubMed] [Google Scholar]
  31. Purkerson J. M., Newberg M., Wise G., Lynch K. R., Isakson P. C. Interleukin 5 and interleukin 2 cooperate with interleukin 4 to induce IgG1 secretion from anti-Ig-treated B cells. J Exp Med. 1988 Sep 1;168(3):1175–1180. doi: 10.1084/jem.168.3.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rothman P., Lutzker S., Cook W., Coffman R., Alt F. W. Mitogen plus interleukin 4 induction of C epsilon transcripts in B lymphoid cells. J Exp Med. 1988 Dec 1;168(6):2385–2389. doi: 10.1084/jem.168.6.2385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sanderson C. J., Campbell H. D., Young I. G. Molecular and cellular biology of eosinophil differentiation factor (interleukin-5) and its effects on human and mouse B cells. Immunol Rev. 1988 Feb;102:29–50. doi: 10.1111/j.1600-065x.1988.tb00740.x. [DOI] [PubMed] [Google Scholar]
  34. Schoenbeck S., McKenzie D. T., Kagnoff M. F. Interleukin 5 is a differentiation factor for IgA B cells. Eur J Immunol. 1989 Jun;19(6):965–969. doi: 10.1002/eji.1830190602. [DOI] [PubMed] [Google Scholar]
  35. Scott P., Natovitz P., Coffman R. L., Pearce E., Sher A. Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med. 1988 Nov 1;168(5):1675–1684. doi: 10.1084/jem.168.5.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Snapper C. M., Finkelman F. D., Paul W. E. Differential regulation of IgG1 and IgE synthesis by interleukin 4. J Exp Med. 1988 Jan 1;167(1):183–196. doi: 10.1084/jem.167.1.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Snapper C. M., Paul W. E. B cell stimulatory factor-1 (interleukin 4) prepares resting murine B cells to secrete IgG1 upon subsequent stimulation with bacterial lipopolysaccharide. J Immunol. 1987 Jul 1;139(1):10–17. [PubMed] [Google Scholar]
  38. Snapper C. M., Paul W. E. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987 May 22;236(4804):944–947. doi: 10.1126/science.3107127. [DOI] [PubMed] [Google Scholar]
  39. Sonoda E., Matsumoto R., Hitoshi Y., Ishii T., Sugimoto M., Araki S., Tominaga A., Yamaguchi N., Takatsu K. Transforming growth factor beta induces IgA production and acts additively with interleukin 5 for IgA production. J Exp Med. 1989 Oct 1;170(4):1415–1420. doi: 10.1084/jem.170.4.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Stavnezer-Nordgren J., Sirlin S. Specificity of immunoglobulin heavy chain switch correlates with activity of germline heavy chain genes prior to switching. EMBO J. 1986 Jan;5(1):95–102. doi: 10.1002/j.1460-2075.1986.tb04182.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Stevens T. L., Bossie A., Sanders V. M., Fernandez-Botran R., Coffman R. L., Mosmann T. R., Vitetta E. S. Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature. 1988 Jul 21;334(6179):255–258. doi: 10.1038/334255a0. [DOI] [PubMed] [Google Scholar]
  42. Suematsu S., Matsuda T., Aozasa K., Akira S., Nakano N., Ohno S., Miyazaki J., Yamamura K., Hirano T., Kishimoto T. IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7547–7551. doi: 10.1073/pnas.86.19.7547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Takatsu K., Tanaka K., Tominaga A., Kumahara Y., Hamaoka T. Antigen-induced T cell-replacing factor (TRF). III. Establishment of T cell hybrid clone continuously producing TRF and functional analysis of released TRF. J Immunol. 1980 Dec;125(6):2646–2653. [PubMed] [Google Scholar]
  44. Teale J. M., Lafrenz D., Klinman N. R., Strober S. Immunoglobulin class commitment exhibited by B lymphocytes separated according to surface isotype. J Immunol. 1981 May;126(5):1952–1957. [PubMed] [Google Scholar]
  45. Teale J. M., Liu F. T., Katz D. H. A clonal analysis of the IgE response and its implications with regard to isotope commitment. J Exp Med. 1981 Apr 1;153(4):783–792. doi: 10.1084/jem.153.4.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tonkonogy S. L., McKenzie D. T., Swain S. L. Regulation of isotype production by IL-4 and IL-5. Effects of lymphokines on Ig production depend on the state of activation of the responding B cells. J Immunol. 1989 Jun 15;142(12):4351–4360. [PubMed] [Google Scholar]
  47. Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253–278. doi: 10.1146/annurev.iy.08.040190.001345. [DOI] [PubMed] [Google Scholar]

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