Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1995 Nov;102(2):389–394. doi: 10.1111/j.1365-2249.1995.tb03795.x

Dual action of IL-4 on mite antigen-induced IgE synthesis in lymphocytes from individuals with bronchial asthma.

Y Kawano 1, T Noma 1
PMCID: PMC1553414  PMID: 7586696

Abstract

Polyclonal IgE synthesis was efficiently induced by Dermatophagoides farinae (Df) antigen in freshly derived peripheral blood lymphocytes from mite-sensitive individuals with bronchial asthma. The in vitro IgE production was significantly correlated with total serum IgE values. The induced IgE synthesis was inhibited in a dose-dependent manner by antibodies to IL-4, indicating a role for endogenous IL-4. Although IL-4 alone increased IgE production, high concentrations (1-100 U/ml) of the cytokine inhibited Df antigen-stimulated production of IgE. However, low concentrations (0.001-0.01 U/ml) of IL-4 significantly enhanced Df antigen-induced IgE production, as did high doses of IL-4 when endogenous IL-4 was neutralized by antibodies to IL-4. Two other cytokines, IL-10 and interferon-gamma (IFN-gamma), showed contrasting actions, as judged from experiments with, exogenous cytokine and anti-cytokine antibodies: IL-10 enhanced and IFN-gamma inhibited Df antigen-induced IgE synthesis. Thus, mite-stimulated IgE production in lymphocytes from individuals with bronchial asthma appears to be regulated by at least three cytokines: IL-4, IL-10, and IFN-gamma.

Full text

PDF
389

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrams J. S., Roncarolo M. G., Yssel H., Andersson U., Gleich G. J., Silver J. E. Strategies of anti-cytokine monoclonal antibody development: immunoassay of IL-10 and IL-5 in clinical samples. Immunol Rev. 1992 Jun;127:5–24. doi: 10.1111/j.1600-065x.1992.tb01406.x. [DOI] [PubMed] [Google Scholar]
  2. Armitage R. J., Macduff B. M., Spriggs M. K., Fanslow W. C. Human B cell proliferation and Ig secretion induced by recombinant CD40 ligand are modulated by soluble cytokines. J Immunol. 1993 May 1;150(9):3671–3680. [PubMed] [Google Scholar]
  3. Aversa G., Punnonen J., Cocks B. G., de Waal Malefyt R., Vega F., Jr, Zurawski S. M., Zurawski G., de Vries J. E. An interleukin 4 (IL-4) mutant protein inhibits both IL-4 or IL-13-induced human immunoglobulin G4 (IgG4) and IgE synthesis and B cell proliferation: support for a common component shared by IL-4 and IL-13 receptors. J Exp Med. 1993 Dec 1;178(6):2213–2218. doi: 10.1084/jem.178.6.2213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  5. Chan S. H., Perussia B., Gupta J. W., Kobayashi M., Pospísil M., Young H. A., Wolf S. F., Young D., Clark S. C., Trinchieri G. Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J Exp Med. 1991 Apr 1;173(4):869–879. doi: 10.1084/jem.173.4.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen P. P., Nonaka M., O'Hair C. H., Cohen P. A., Zuraw B. L., Katz D. H. Human IgE synthesis in vitro by pokeweed mitogen-stimulated human lymphoid cells: verification with a reconfirmed epsilon-specific radioimmunoassay. J Immunol. 1984 Oct;133(4):1909–1913. [PubMed] [Google Scholar]
  7. Defrance T., Vanbervliet B., Brière F., Durand I., Rousset F., Banchereau J. Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A. J Exp Med. 1992 Mar 1;175(3):671–682. doi: 10.1084/jem.175.3.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Del Prete G., Maggi E., Parronchi P., Chrétien I., Tiri A., Macchia D., Ricci M., Banchereau J., De Vries J., Romagnani S. IL-4 is an essential factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants. J Immunol. 1988 Jun 15;140(12):4193–4198. [PubMed] [Google Scholar]
  9. Fluckiger A. C., Garrone P., Durand I., Galizzi J. P., Banchereau J. Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes. J Exp Med. 1993 Nov 1;178(5):1473–1481. doi: 10.1084/jem.178.5.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jelinek D. F., Lipsky P. E. Inhibitory influence of IL-4 on human B cell responsiveness. J Immunol. 1988 Jul 1;141(1):164–173. [PubMed] [Google Scholar]
  11. Kiniwa M., Gately M., Gubler U., Chizzonite R., Fargeas C., Delespesse G. Recombinant interleukin-12 suppresses the synthesis of immunoglobulin E by interleukin-4 stimulated human lymphocytes. J Clin Invest. 1992 Jul;90(1):262–266. doi: 10.1172/JCI115846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kotowicz K., Callard R. E. Human immunoglobulin class and IgG subclass regulation: dual action of interleukin-4. Eur J Immunol. 1993 Sep;23(9):2250–2256. doi: 10.1002/eji.1830230930. [DOI] [PubMed] [Google Scholar]
  13. Llorente L., Crevon M. C., Karray S., Defrance T., Banchereau J., Galanaud P. Interleukin (IL) 4 counteracts the helper effect of IL2 on antigen-activated human B cells. Eur J Immunol. 1989 Apr;19(4):765–769. doi: 10.1002/eji.1830190429. [DOI] [PubMed] [Google Scholar]
  14. Manetti R., Parronchi P., Giudizi M. G., Piccinni M. P., Maggi E., Trinchieri G., Romagnani S. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med. 1993 Apr 1;177(4):1199–1204. doi: 10.1084/jem.177.4.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miyamoto T., Johansson S. G., Ito K., Horiuchi Y. Atopic allergy in Japanese subjects: studies primarily with radioallergosorbent test. J Allergy Clin Immunol. 1974 Jan;53(1):9–19. doi: 10.1016/0091-6749(74)90094-3. [DOI] [PubMed] [Google Scholar]
  16. O'Hehir R. E., Bal V., Quint D., Moqbel R., Kay A. B., Zanders E. D., Lamb J. R. An in vitro model of allergen-dependent IgE synthesis by human B lymphocytes: comparison of the response of an atopic and a non-atopic individual to Dermatophagoides spp. (house dust mite). Immunology. 1989 Apr;66(4):499–504. [PMC free article] [PubMed] [Google Scholar]
  17. Parronchi P., Macchia D., Piccinni M. P., Biswas P., Simonelli C., Maggi E., Ricci M., Ansari A. A., Romagnani S. Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4538–4542. doi: 10.1073/pnas.88.10.4538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pryjma J., Muñoz J., Virella G., Fudenberg H. H. Evaluation of IgM, IgG, IgA, IgD, and IgE secretion by human peripheral blood lymphocytes in cultures stimulated with pokeweed mitogen and Staphylococcus aureus Cowan I. Cell Immunol. 1980 Mar 1;50(1):115–124. doi: 10.1016/0008-8749(80)90011-8. [DOI] [PubMed] [Google Scholar]
  19. Punnonen J., Aversa G., Cocks B. G., McKenzie A. N., Menon S., Zurawski G., de Waal Malefyt R., de Vries J. E. Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3730–3734. doi: 10.1073/pnas.90.8.3730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Punnonen J., de Waal Malefyt R., van Vlasselaer P., Gauchat J. F., de Vries J. E. IL-10 and viral IL-10 prevent IL-4-induced IgE synthesis by inhibiting the accessory cell function of monocytes. J Immunol. 1993 Aug 1;151(3):1280–1289. [PubMed] [Google Scholar]
  21. Pène J., Rousset F., Brière F., Chrétien I., Bonnefoy J. Y., Spits H., Yokota T., Arai N., Arai K., Banchereau J. IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6880–6884. doi: 10.1073/pnas.85.18.6880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pène J., Rousset F., Brière F., Chrétien I., Paliard X., Banchereau J., Spits H., De Vries J. E. IgE production by normal human B cells induced by alloreactive T cell clones is mediated by IL-4 and suppressed by IFN-gamma. J Immunol. 1988 Aug 15;141(4):1218–1224. [PubMed] [Google Scholar]
  23. Rousset F., Garcia E., Defrance T., Péronne C., Vezzio N., Hsu D. H., Kastelein R., Moore K. W., Banchereau J. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1890–1893. doi: 10.1073/pnas.89.5.1890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Saxon A., Stevens R. H. Stimulation and regulation of human IgE production in vitro using peripheral blood lymphocytes. Clin Immunol Immunopathol. 1979 Dec;14(4):474–488. doi: 10.1016/0090-1229(79)90100-4. [DOI] [PubMed] [Google Scholar]
  25. Spiegelberg H. L., Falkoff R. J., O'Connor R. D., Beck L. Interleukin-2 inhibits the interleukin-4-induced human IgE and IgG4 secretion in vivo. Clin Exp Immunol. 1991 Jun;84(3):400–405. [PMC free article] [PubMed] [Google Scholar]
  26. Vercelli D., Jabara H. H., Arai K., Geha R. S. Induction of human IgE synthesis requires interleukin 4 and T/B cell interactions involving the T cell receptor/CD3 complex and MHC class II antigens. J Exp Med. 1989 Apr 1;169(4):1295–1307. doi: 10.1084/jem.169.4.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wierenga E. A., Snoek M., de Groot C., Chrétien I., Bos J. D., Jansen H. M., Kapsenberg M. L. Evidence for compartmentalization of functional subsets of CD2+ T lymphocytes in atopic patients. J Immunol. 1990 Jun 15;144(12):4651–4656. [PubMed] [Google Scholar]
  28. Yang X. D., De Weck A. L., Stadler B. M. Effect of recombinant human interleukin 4 on spontaneous in vitro human IgE synthesis. Eur J Immunol. 1988 Nov;18(11):1699–1704. doi: 10.1002/eji.1830181107. [DOI] [PubMed] [Google Scholar]
  29. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES