Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1993 Mar;61(3):1105–1112. doi: 10.1128/iai.61.3.1105-1112.1993

Induction of murine T-helper-cell responses to the filarial nematode Brugia malayi.

E Pearlman 1, F E Hazlett Jr 1, W H Boom 1, J W Kazura 1
PMCID: PMC302845  PMID: 8094378

Abstract

The purpose of this study was to examine the murine T-helper-cell (Th) cytokine response to the human filarial parasite Brugia malayi. In the first 14 days following intraperitoneal inoculation of live microfilariae into BALB/c mice, filarial antigen-driven splenic lymphoid cells produced gamma interferon (IFN-gamma) and little or no interleukin-5 (IL-5). After this time, IL-5 production increased (to 10 to 12 ng per 5 x 10(6) cells) coincident with a marked diminution in IFN-gamma generation. A single subcutaneous immunization with soluble microfilarial antigens also induced an IFN-gamma but no IL-5 response, whereas immunization three times elicited a predominant Th2-like reaction characterized by IL-4 and IL-5 production by CD4+ lymph node lymphocytes and a 10-fold increase in serum immunoglobulin E. The importance of IL-10 in establishing the balance between parasite-specific Th1 and Th2 responses was demonstrated by the ability of neutralizing monoclonal antibody to this cytokine to increase IFN-gamma production by splenic and lymph node cells from mice chronically exposed to live microfilariae or immunized multiple times with soluble filarial antigens.

Full text

PDF
1105

Selected References

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

  1. Baniyash M., Eshhar Z. Inhibition of IgE binding to mast cells and basophils by monoclonal antibodies to murine IgE. Eur J Immunol. 1984 Sep;14(9):799–807. doi: 10.1002/eji.1830140907. [DOI] [PubMed] [Google Scholar]
  2. Boom W. H., Liebster L., Abbas A. K., Titus R. G. Patterns of cytokine secretion in murine leishmaniasis: correlation with disease progression or resolution. Infect Immun. 1990 Dec;58(12):3863–3870. doi: 10.1128/iai.58.12.3863-3870.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Byars N. E., Allison A. C. Adjuvant formulation for use in vaccines to elicit both cell-mediated and humoral immunity. Vaccine. 1987 Sep;5(3):223–228. doi: 10.1016/0264-410x(87)90105-8. [DOI] [PubMed] [Google Scholar]
  4. Chang T. L., Shea C. M., Urioste S., Thompson R. C., Boom W. H., Abbas A. K. Heterogeneity of helper/inducer T lymphocytes. III. Responses of IL-2- and IL-4-producing (Th1 and Th2) clones to antigens presented by different accessory cells. J Immunol. 1990 Nov 1;145(9):2803–2808. [PubMed] [Google Scholar]
  5. Clutterbuck E. J., Hirst E. M., Sanderson C. J. Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF. Blood. 1989 May 1;73(6):1504–1512. [PubMed] [Google Scholar]
  6. 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]
  7. Del Prete G. F., De Carli M., Mastromauro C., Biagiotti R., Macchia D., Falagiani P., Ricci M., Romagnani S. Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. J Clin Invest. 1991 Jul;88(1):346–350. doi: 10.1172/JCI115300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Else K. J., Grencis R. K. Cellular immune responses to the murine nematode parasite Trichuris muris. I. Differential cytokine production during acute or chronic infection. Immunology. 1991 Apr;72(4):508–513. [PMC free article] [PubMed] [Google Scholar]
  9. Else K. J., Hültner L., Grencis R. K. Cellular immune responses to the murine nematode parasite Trichuris muris. II. Differential induction of TH-cell subsets in resistant versus susceptible mice. Immunology. 1992 Feb;75(2):232–237. [PMC free article] [PubMed] [Google Scholar]
  10. Fanning M. M., Kazura J. W. Further studies on genetic variation of hepatosplenic disease and modulation in murine schistosomiasis mansoni. Parasite Immunol. 1985 May;7(3):213–222. doi: 10.1111/j.1365-3024.1985.tb00071.x. [DOI] [PubMed] [Google Scholar]
  11. Fanning M. M., Peters P. A., Davis R. S., Kazura J. W., Mahmoud A. A. Immunopathology of murine infection with Schistosoma mansoni: relationship of genetic background to hepatosplenic disease and modulation. J Infect Dis. 1981 Aug;144(2):148–153. doi: 10.1093/infdis/144.2.148. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Fiorentino D. F., Bond M. W., Mosmann T. R. 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. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gajewski T. F., Fitch F. W. 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] [Google Scholar]
  15. Gajewski T. F., Pinnas M., Wong T., Fitch F. W. 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] [Google Scholar]
  16. Gascan H., Gauchat J. F., de Waal Malefyt R., Schneider P., Yssel H., de Vries J. E. Regulation of human IgE synthesis. Clin Exp Allergy. 1991 Jan;21 (Suppl 1):162–166. doi: 10.1111/j.1365-2222.1991.tb01721.x. [DOI] [PubMed] [Google Scholar]
  17. Grencis R. K., Hültner L., Else K. J. Host protective immunity to Trichinella spiralis in mice: activation of Th cell subsets and lymphokine secretion in mice expressing different response phenotypes. Immunology. 1991 Oct;74(2):329–332. [PMC free article] [PubMed] [Google Scholar]
  18. Grzych J. M., Pearce E., Cheever A., Caulada Z. A., Caspar P., Heiny S., Lewis F., Sher A. Egg deposition is the major stimulus for the production of Th2 cytokines in murine schistosomiasis mansoni. J Immunol. 1991 Feb 15;146(4):1322–1327. [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. Herzenberg L. A., Stall A. M., Lalor P. A., Sidman C., Moore W. A., Parks D. R., Herzenberg L. A. The Ly-1 B cell lineage. Immunol Rev. 1986 Oct;93:81–102. doi: 10.1111/j.1600-065x.1986.tb01503.x. [DOI] [PubMed] [Google Scholar]
  21. Kazura J. W., Cicirello H., McCall J. W. Induction of protection against Brugia malayi infection in jirds by microfilarial antigens. J Immunol. 1986 Feb 15;136(4):1422–1426. [PubMed] [Google Scholar]
  22. Kazura J. W., Davis R. S. Soluble Brugia malayi microfilarial antigens protect mice against challenge by an antibody-dependent mechanism. J Immunol. 1982 Apr;128(4):1792–1796. [PubMed] [Google Scholar]
  23. Kelly E. A., Cruz E. S., Hauda K. M., Wassom D. L. IFN-gamma- and IL-5-producing cells compartmentalize to different lymphoid organs in Trichinella spiralis-infected mice. J Immunol. 1991 Jul 1;147(1):306–311. [PubMed] [Google Scholar]
  24. King C. L., Kumaraswami V., Poindexter R. W., Kumari S., Jayaraman K., Alling D. W., Ottesen E. A., Nutman T. B. Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state. J Clin Invest. 1992 May;89(5):1403–1410. doi: 10.1172/JCI115729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lok J. B., Abraham D. Animal models for the study of immunity in human filariasis. Parasitol Today. 1992 May;8(5):168–171. doi: 10.1016/0169-4758(92)90014-s. [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., Fong T. A. Specific assays for cytokine production by T cells. J Immunol Methods. 1989 Jan 17;116(2):151–158. doi: 10.1016/0022-1759(89)90198-1. [DOI] [PubMed] [Google Scholar]
  28. Mosmann T. R., Schumacher J. H., Fiorentino D. F., Leverah J., Moore K. W., Bond M. W. Isolation of monoclonal antibodies specific for IL-4, IL-5, IL-6, and a new Th2-specific cytokine (IL-10), cytokine synthesis inhibitory factor, by using a solid phase radioimmunoadsorbent assay. J Immunol. 1990 Nov 1;145(9):2938–2945. [PubMed] [Google Scholar]
  29. O'Garra A., Chang R., Go N., Hastings R., Haughton G., Howard M. Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10. Eur J Immunol. 1992 Mar;22(3):711–717. doi: 10.1002/eji.1830220314. [DOI] [PubMed] [Google Scholar]
  30. Ottesen E. A. The Wellcome Trust Lecture. Infection and disease in lymphatic filariasis: an immunological perspective. Parasitology. 1992;104 (Suppl):S71–S79. doi: 10.1017/s0031182000075259. [DOI] [PubMed] [Google Scholar]
  31. Pearce E. J., Caspar P., Grzych J. M., Lewis F. A., 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. doi: 10.1084/jem.173.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Piessens W. F., Partono F., Hoffman S. L., Ratiwayanto S., Piessens P. W., Palmieri J. R., Koiman I., Dennis D. T., Carney W. P. Antigen-specific suppressor T lymphocytes in human lymphatic filariasis. N Engl J Med. 1982 Jul 15;307(3):144–148. doi: 10.1056/NEJM198207153070302. [DOI] [PubMed] [Google Scholar]
  33. Piessens W. F., Ratiwayanto S., Tuti S., Palmieri J. H., Piessens P. W., Koiman I., Dennis D. T. Antigen-specific suppressor cells and suppressor factors in human filariasis with Brugia malayi. N Engl J Med. 1980 Apr 10;302(15):833–837. doi: 10.1056/NEJM198004103021503. [DOI] [PubMed] [Google Scholar]
  34. Sadick M. D., Heinzel F. P., Holaday B. J., Pu R. T., Dawkins R. S., Locksley R. M. Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism. J Exp Med. 1990 Jan 1;171(1):115–127. doi: 10.1084/jem.171.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schumacher J. H., O'Garra A., Shrader B., van Kimmenade A., Bond M. W., Mosmann T. R., Coffman R. L. The characterization of four monoclonal antibodies specific for mouse IL-5 and development of mouse and human IL-5 enzyme-linked immunosorbent. J Immunol. 1988 Sep 1;141(5):1576–1581. [PubMed] [Google Scholar]
  36. Scott P. IFN-gamma modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. J Immunol. 1991 Nov 1;147(9):3149–3155. [PubMed] [Google Scholar]
  37. Sher A., Fiorentino D., Caspar P., Pearce E., Mosmann T. Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection. J Immunol. 1991 Oct 15;147(8):2713–2716. [PubMed] [Google Scholar]
  38. Silva J. S., Morrissey P. J., Grabstein K. H., Mohler K. M., Anderson D., Reed S. G. Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection. J Exp Med. 1992 Jan 1;175(1):169–174. doi: 10.1084/jem.175.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Street N. E., Mosmann T. R. Functional diversity of T lymphocytes due to secretion of different cytokine patterns. FASEB J. 1991 Feb;5(2):171–177. doi: 10.1096/fasebj.5.2.1825981. [DOI] [PubMed] [Google Scholar]
  40. Vella A. T., Pearce E. J. CD4+ Th2 response induced by Schistosoma mansoni eggs develops rapidly, through an early, transient, Th0-like stage. J Immunol. 1992 Apr 1;148(7):2283–2290. [PubMed] [Google Scholar]
  41. Weaver C. T., Hawrylowicz C. M., Unanue E. R. 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. doi: 10.1073/pnas.85.21.8181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wierenga E. A., Snoek M., Jansen H. M., Bos J. D., van Lier R. A., Kapsenberg M. L. Human atopen-specific types 1 and 2 T helper cell clones. J Immunol. 1991 Nov 1;147(9):2942–2949. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES