Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1994 Nov 1;180(5):1793–1803. doi: 10.1084/jem.180.5.1793

Evidence for an interleukin 4-inducible immunoglobulin E uptake and transport mechanism in the intestine

PMCID: PMC2191712  PMID: 7964461

Abstract

Immunoglobulin (Ig) E is the principal Ig involved in immediate hypersensitivities and chronic allergic diseases such as asthma. Helminths are the most potent infectious agents known for their capacity to stimulate IgE production during the course of infection. In rats, the nematode Trichinella spiralis typically elicits a strong parasite-specific IgE response during infection, and this IgE antibody has been shown to be protective against the parasite in passive transfer experiments. The study reported here analyzed the fate of 125I- labeled myeloma IgE (1R162) in normal and T. spiralis-infected rats after intravenous injection. T. spiralis infection induced a capacity for specific binding to the gut wall of 125I-IgE rather than 125I-IgG1, as well as the transport of IgE, but not IgG1, into the gut lumen. Peak intestinal uptake and transport of 125I-IgE occurred during the first and second weeks after injection but was not elevated in the fourth week, that is, after intestinal adult worms had been expelled. Neither 125I-IgE uptake in the gut wall nor transport to the lumen could be ascribed to tissue damage or vascular leakage. Luminal transport occurred in the small intestine and not the liver, which only transports low molecular weight degraded 125I-IgE. Calculations based on the amount of intact IgE in the lumen suggest that, in a 24-h period, up to 20% of injected 125I-IgE can be transported to the gut lumen during the peak transport period, between 6 and 14 d after infection. The intestinal IgE binding and transport response can be adoptively transferred with T. spiralis immune CD4+ OX22- (CD45RC-) lymphocytes, which are protective, but not the nonprotective sister population CD4+ OX22+ (CD45RC+) of lymphocytes isolated simultaneously from thoracic duct lymph of infected rats. The intravenous infusion of recombinant rat interleukin 4 also elicited significant intestinal uptake of 125I-IgE. We also present evidence for the presence of CD23 on rat intraepithelial lymphocytes. These data provide evidence for a novel, inducible, intestine-specific IgE uptake and transport mechanism.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Ahmad A., Wang C. H., Bell R. G. A role for IgE in intestinal immunity. Expression of rapid expulsion of Trichinella spiralis in rats transfused with IgE and thoracic duct lymphocytes. J Immunol. 1991 May 15;146(10):3563–3570. [PubMed] [Google Scholar]
  2. Ahmad A., Wang C. H., Korenaga M., Bell R. G., Adams L. S. Synergistic interaction between immune serum and thoracic duct cells in the adoptive transfer of rapid expulsion of Trichinella spiralis in adult rats. Exp Parasitol. 1990 Jul;71(1):90–99. doi: 10.1016/0014-4894(90)90011-z. [DOI] [PubMed] [Google Scholar]
  3. Alizadeh H., Urban J. F., Jr, Katona I. M., Finkelman F. D. Cells containing IgE in the intestinal mucosa of mice infected with the nematode parasite Trichinella spiralis are predominantly of a mast cell lineage. J Immunol. 1986 Oct 15;137(8):2555–2560. [PubMed] [Google Scholar]
  4. Barnes P. J. Biochemistry of asthma. Trends Biochem Sci. 1991 Oct;16(10):365–369. doi: 10.1016/0968-0004(91)90152-l. [DOI] [PubMed] [Google Scholar]
  5. Basciano L. K., Berenstein E. H., Kmak L., Siraganian R. P. Monoclonal antibodies that inhibit IgE binding. J Biol Chem. 1986 Sep 5;261(25):11823–11831. [PubMed] [Google Scholar]
  6. Befus A. D., Spencer J. A., McDermott M. R., McLaughlin B., Bienenstock J. Isolation and characteristics of small intestinal lamina propria cells from normal and nematode (Nippostrongylus brasiliensis)-infected rats. Int Arch Allergy Appl Immunol. 1984;75(4):345–350. doi: 10.1159/000233645. [DOI] [PubMed] [Google Scholar]
  7. Bell R. G., Appleton J. A., Negrao-Correa D. A., Adams L. S. Rapid expulsion of Trichinella spiralis in adult rats mediated by monoclonal antibodies of distinct IgG isotypes. Immunology. 1992 Mar;75(3):520–527. [PMC free article] [PubMed] [Google Scholar]
  8. Bell R. G., Korenaga M., Wang C. H. Characterization of a cell population in thoracic duct lymph that adoptively transfers rejection of adult Trichinella spiralis to normal rats. Immunology. 1987 Jun;61(2):221–227. [PMC free article] [PubMed] [Google Scholar]
  9. Belut D., Moneret-Vautrin D. A., Nicolas J. P., Grilliat J. P. IgE levels in intestinal juice. Dig Dis Sci. 1980 May;25(5):323–332. doi: 10.1007/BF01308055. [DOI] [PubMed] [Google Scholar]
  10. Bieber T., de la Salle H., Wollenberg A., Hakimi J., Chizzonite R., Ring J., Hanau D., de la Salle C. Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI). J Exp Med. 1992 May 1;175(5):1285–1290. doi: 10.1084/jem.175.5.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Brandtzaeg P. Human secretory component--VI. Immunoglobulin-binding properities. Immunochemistry. 1977 Mar;14(3):179–188. doi: 10.1016/0019-2791(77)90192-6. [DOI] [PubMed] [Google Scholar]
  12. Brassart D., Kolodziejczyk E., Granato D., Woltz A., Pavillard M., Perotti F., Frigeri L. G., Liu F. T., Borel Y., Neeser J. R. An intestinal galactose-specific lectin mediates the binding of murine IgE to mouse intestinal epithelial cells. Eur J Biochem. 1992 Feb 1;203(3):393–399. doi: 10.1111/j.1432-1033.1992.tb16563.x. [DOI] [PubMed] [Google Scholar]
  13. Brideau R. J., Carter P. B., McMaster W. R., Mason D. W., Williams A. F. Two subsets of rat T lymphocytes defined with monoclonal antibodies. Eur J Immunol. 1980 Aug;10(8):609–615. doi: 10.1002/eji.1830100807. [DOI] [PubMed] [Google Scholar]
  14. Brown W. R., Lee E. H. Studies on IgE in human intestinal fluids. Int Arch Allergy Appl Immunol. 1976;50(1):87–94. doi: 10.1159/000231483. [DOI] [PubMed] [Google Scholar]
  15. Conrad D. H., Studer E., Gervasoni J., Mohanakumar T. Properties of two monoclonal antibodies directed against the Fc and Fab' regions of rat IgE. Int Arch Allergy Appl Immunol. 1983;70(4):352–360. doi: 10.1159/000233347. [DOI] [PubMed] [Google Scholar]
  16. Dreskin S. C., Goldsmith P. K., Strober W., Zech L. A., Gallin J. I. Metabolism of immunoglobulin E in patients with markedly elevated serum immunoglobulin E levels. J Clin Invest. 1987 Jun;79(6):1764–1772. doi: 10.1172/JCI113017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dunne D. W., Butterworth A. E., Fulford A. J., Kariuki H. C., Langley J. G., Ouma J. H., Capron A., Pierce R. J., Sturrock R. F. Immunity after treatment of human schistosomiasis: association between IgE antibodies to adult worm antigens and resistance to reinfection. Eur J Immunol. 1992 Jun;22(6):1483–1494. doi: 10.1002/eji.1830220622. [DOI] [PubMed] [Google Scholar]
  18. Foster D. O., Frydman M. L. Nonshivering thermogenesis in the rat. II. Measurements of blood flow with microspheres point to brown adipose tissue as the dominant site of the calorigenesis induced by noradrenaline. Can J Physiol Pharmacol. 1978 Feb;56(1):110–122. doi: 10.1139/y78-015. [DOI] [PubMed] [Google Scholar]
  19. Freier S., Lebenthal E., Freier M., Shah P. C., Park B. H., Lee P. C. IgE and IgD antibodies to cow milk and soy protein in duodenal fluid: effects of pancreozymin and secretin. Immunology. 1983 May;49(1):69–75. [PMC free article] [PubMed] [Google Scholar]
  20. Gounni A. S., Lamkhioued B., Ochiai K., Tanaka Y., Delaporte E., Capron A., Kinet J. P., Capron M. High-affinity IgE receptor on eosinophils is involved in defence against parasites. Nature. 1994 Jan 13;367(6459):183–186. doi: 10.1038/367183a0. [DOI] [PubMed] [Google Scholar]
  21. Hagan P. IgE and protective immunity to helminth infections. Parasite Immunol. 1993 Jan;15(1):1–4. doi: 10.1111/j.1365-3024.1993.tb00565.x. [DOI] [PubMed] [Google Scholar]
  22. Hakimi J., Seals C., Kondas J. A., Pettine L., Danho W., Kochan J. The alpha subunit of the human IgE receptor (FcERI) is sufficient for high affinity IgE binding. J Biol Chem. 1990 Dec 25;265(36):22079–22081. [PubMed] [Google Scholar]
  23. Hobday J. D., Cake M., Turner K. J. A comparison of the immunoglobulins IgA, IgG and IgE in nasal secretions from normal and asthmatic children. Clin Exp Immunol. 1971 Nov;9(5):577–583. [PMC free article] [PubMed] [Google Scholar]
  24. Iio A., Waldmann T. A., Strober W. Metabolic study of human IgE: evidence for an extravascular catabolic pathway. J Immunol. 1978 May;120(5):1696–1701. [PubMed] [Google Scholar]
  25. Ishizaka K., Newcomb R. W. Presence of gammaE in nasal washings and sputum from asthmatic patients. J Allergy. 1970 Oct;46(4):197–204. doi: 10.1016/0021-8707(70)90023-7. [DOI] [PubMed] [Google Scholar]
  26. Ishizaka T., Urban J. F., Jr, Ishizaka K. IgE formation in the rat following infection with Nippostrongylus brasiliensis. I. Proliferation and differentiation of IgE-bearing cells. Cell Immunol. 1976 Mar 15;22(2):248–261. doi: 10.1016/0008-8749(76)90027-7. [DOI] [PubMed] [Google Scholar]
  27. Jackson G. D., Lemaître-Coelho I., Vaerman J. P., Bazin H., Beckers A. Rapid disappearance from serum of intravenously injected rat myeloma IgA and its secretion into bile. Eur J Immunol. 1978 Feb;8(2):123–126. doi: 10.1002/eji.1830080210. [DOI] [PubMed] [Google Scholar]
  28. Jarrett E., Bazin H. Elevation of total serum IgE in rats following helminth parasite infection. Nature. 1974 Oct 18;251(5476):613–614. doi: 10.1038/251613a0. [DOI] [PubMed] [Google Scholar]
  29. Johansson S. G., Mellbin T., Vahlquist B. Immunoglobulin levels in Ethiopian preschool children with special reference to high concentrations of immunoglobulin E (IgND). Lancet. 1968 May 25;1(7552):1118–1121. doi: 10.1016/s0140-6736(68)90187-6. [DOI] [PubMed] [Google Scholar]
  30. Jonard P. P., Rambaud J. C., Dive C., Vaerman J. P., Galian A., Delacroix D. L. Secretion of immunoglobulins and plasma proteins from the jejunal mucosa. Transport rate and origin of polymeric immunoglobulin A. J Clin Invest. 1984 Aug;74(2):525–535. doi: 10.1172/JCI111450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Joseph M., Auriault C., Capron A., Vorng H., Viens P. A new function for platelets: IgE-dependent killing of schistosomes. Nature. 1983 Jun 30;303(5920):810–812. doi: 10.1038/303810a0. [DOI] [PubMed] [Google Scholar]
  32. Kaiserlian D., Lachaux A., Grosjean I., Graber P., Bonnefoy J. Y. Intestinal epithelial cells express the CD23/Fc epsilon RII molecule: enhanced expression in enteropathies. Immunology. 1993 Sep;80(1):90–95. [PMC free article] [PubMed] [Google Scholar]
  33. Kaplan J. E., Larrick J. W., Yost J. A. Hyperimmunoglobulinemia E in the Waorani, an isolated Amerindian population. Am J Trop Med Hyg. 1980 Sep;29(5):1012–1017. doi: 10.4269/ajtmh.1980.29.1012. [DOI] [PubMed] [Google Scholar]
  34. Korenaga M., Wang C. H., Bell R. G., Zhu D., Ahmad A. Intestinal immunity to Trichinella spiralis is a property of OX8- OX22- T-helper cells that are generated in the intestine. Immunology. 1989 Apr;66(4):588–594. [PMC free article] [PubMed] [Google Scholar]
  35. LARSH J. E., Jr, RACE G. J. A histopathologic study of the anterior small intestine of immunized and nonimmunized mice infected with Trichinella spiralis. J Infect Dis. 1954 May-Jun;94(3):262–272. doi: 10.1093/infdis/94.3.262. [DOI] [PubMed] [Google Scholar]
  36. Lee T. D., Shanahan F., Miller H. R., Bienenstock J., Befus A. D. Intestinal mucosal mast cells: isolation from rat lamina propria and purification using unit gravity velocity sedimentation. Immunology. 1985 Aug;55(4):721–728. [PMC free article] [PubMed] [Google Scholar]
  37. Lynch N. R., Hagel I., Perez M., Di Prisco M. C., Lopez R., Alvarez N. Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum. J Allergy Clin Immunol. 1993 Sep;92(3):404–411. doi: 10.1016/0091-6749(93)90119-z. [DOI] [PubMed] [Google Scholar]
  38. Lynch N. R., López R., Istúriz G., Tenías-Salazar E. Allergic reactivity and helminthic infection in Amerindians of the Amazon Basin. Int Arch Allergy Appl Immunol. 1983;72(4):369–372. doi: 10.1159/000234899. [DOI] [PubMed] [Google Scholar]
  39. Mayrhofer G., Bazin H., Gowans J. L. Nature of cells binding anti-IgE in rats immunized with Nippostrongylus brasiliensis: IgE synthesis in regional nodes and concentration in mucosal mast cells. Eur J Immunol. 1976 Aug;6(8):537–545. doi: 10.1002/eji.1830060803. [DOI] [PubMed] [Google Scholar]
  40. McKnight A. J., Classon B. J. Biochemical and immunological properties of rat recombinant interleukin-2 and interleukin-4. Immunology. 1992 Feb;75(2):286–292. [PMC free article] [PubMed] [Google Scholar]
  41. Merrett T. G., Merrett J., Cookson J. B. Allergy and parasites: the measurement of total and specific IgE levels in urban and rural communities in Rhodesia. Clin Allergy. 1976 Mar;6(2):131–134. doi: 10.1111/j.1365-2222.1976.tb01890.x. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Nakajima S., Gillespie D. N., Gleich G. J. Differences between IgA and IgE as secretory proteins. Clin Exp Immunol. 1975 Aug;21(2):306–317. [PMC free article] [PubMed] [Google Scholar]
  44. Newcomb R. W., Ishizaka K. Physicochemical and antigenic studies on human gamma E in respiratory fluid. J Immunol. 1970 Jul;105(1):85–89. [PubMed] [Google Scholar]
  45. Ottaway C. A., Manson-Smith D. F., Bruce R. G., Parrott D. M. Regional blood flow and the localization of lymphoblasts in the small intestine of the mouse. II. The effects of a primary enteric infection with Trichinella spiralis. Immunology. 1980 Dec;41(4):963–971. [PMC free article] [PubMed] [Google Scholar]
  46. Pritchard D. I. Immunity to helminths: is too much IgE parasite--rather than host-protective? Parasite Immunol. 1993 Jan;15(1):5–9. doi: 10.1111/j.1365-3024.1993.tb00566.x. [DOI] [PubMed] [Google Scholar]
  47. Ramaswamy K., Goodman R. E., Bell R. G. Cytokine profile of protective anti-Trichinella spiralis CD4+ OX22- and non-protective CD4+ OX22+ thoracic duct cells in rats: secretion of IL-4 alone does not determine protective capacity. Parasite Immunol. 1994 Aug;16(8):435–445. doi: 10.1111/j.1365-3024.1994.tb00371.x. [DOI] [PubMed] [Google Scholar]
  48. Salacinski P. R., McLean C., Sykes J. E., Clement-Jones V. V., Lowry P. J. Iodination of proteins, glycoproteins, and peptides using a solid-phase oxidizing agent, 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenyl glycoluril (Iodogen). Anal Biochem. 1981 Oct;117(1):136–146. doi: 10.1016/0003-2697(81)90703-x. [DOI] [PubMed] [Google Scholar]
  49. Savilahti E. Immunoglobulin-containing cells in the intestinal mucosa and immunoglobulins in the intestinal juice in children. Clin Exp Immunol. 1972 Jul;11(3):415–425. [PMC free article] [PubMed] [Google Scholar]
  50. 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]
  51. Spickett G. P., Brandon M. R., Mason D. W., Williams A. F., Woollett G. R. MRC OX-22, a monoclonal antibody that labels a new subset of T lymphocytes and reacts with the high molecular weight form of the leukocyte-common antigen. J Exp Med. 1983 Sep 1;158(3):795–810. doi: 10.1084/jem.158.3.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Springer T. A., Bhattacharya A., Cardoza J. T., Sanchez-Madrid F. Monoclonal antibodies specific for rat IgG1, IgG2a, and IgG2b subclasses, and kappa chain monotypic and allotypic determinants: reagents for use with rat monoclonal antibodies. Hybridoma. 1982;1(3):257–273. doi: 10.1089/hyb.1.1982.1.257. [DOI] [PubMed] [Google Scholar]
  53. Spry C. J., Kay A. B., Gleich G. J. Eosinophils 1992. Immunol Today. 1992 Oct;13(10):384–387. doi: 10.1016/0167-5699(92)90085-L. [DOI] [PubMed] [Google Scholar]
  54. Stevens R. L., Austen K. F. Recent advances in the cellular and molecular biology of mast cells. Immunol Today. 1989 Nov;10(11):381–386. doi: 10.1016/0167-5699(89)90272-7. [DOI] [PubMed] [Google Scholar]
  55. Tada T., Ishizaka K. Distribution of gamma E-forming cells in lymphoid tissues of the human and monkey. J Immunol. 1970 Feb;104(2):377–387. [PubMed] [Google Scholar]
  56. Tada T., Okumura K., Platteau B., Beckers A., Bazin H. Half-lives of two types of rat homocytotropic antibodies in circulation and in the skin. Int Arch Allergy Appl Immunol. 1975;48(1):116–131. doi: 10.1159/000231297. [DOI] [PubMed] [Google Scholar]
  57. Turner K. J., Feddema L., Quinn E. H. Non-specific potentiation of IgE by parasitic infections in man. Int Arch Allergy Appl Immunol. 1979;58(2):232–236. doi: 10.1159/000232197. [DOI] [PubMed] [Google Scholar]
  58. Underdown B. J., Knight A., Papsin F. R. The relative paucity of IgE in human milk. J Immunol. 1976 May;116(5):1435–1438. [PubMed] [Google Scholar]
  59. Wang B., Rieger A., Kilgus O., Ochiai K., Maurer D., Födinger D., Kinet J. P., Stingl G. Epidermal Langerhans cells from normal human skin bind monomeric IgE via Fc epsilon RI. J Exp Med. 1992 May 1;175(5):1353–1365. doi: 10.1084/jem.175.5.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Wang C. H., Korenaga M., Greenwood A., Bell R. G. T-helper subset function in the gut of rats: differential stimulation of eosinophils, mucosal mast cells and antibody-forming cells by OX8- OX22- and OX8- OX22+ cells. Immunology. 1990 Oct;71(2):166–175. [PMC free article] [PubMed] [Google Scholar]
  61. Wright K. A., Weidman E., Hong H. The distribution of cells killed by Trichinella spiralis in the mucosal epithelium of two strains of mice. J Parasitol. 1987 Oct;73(5):935–939. [PubMed] [Google Scholar]
  62. Wüthrich B. Epidemiology of the allergic diseases: are they really on the increase? Int Arch Allergy Appl Immunol. 1989;90 (Suppl 1):3–10. doi: 10.1159/000235067. [DOI] [PubMed] [Google Scholar]
  63. Zhu D. Z., Bell R. G. Trichinella spiralis: murine strain variation in response to monoclonally defined, protective, nonstage-specific antigens. Exp Parasitol. 1990 Apr;70(3):330–343. doi: 10.1016/0014-4894(90)90115-s. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES