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. 1994 Mar;62(3):818–827. doi: 10.1128/iai.62.3.818-827.1994

CD4+ T-cell clones obtained from cattle chronically infected with Fasciola hepatica and specific for adult worm antigen express both unrestricted and Th2 cytokine profiles.

W C Brown 1, W C Davis 1, D A Dobbelaere 1, A C Rice-Ficht 1
PMCID: PMC186188  PMID: 7509319

Abstract

The well-established importance of helper T (Th)-cell subsets in immunity and immunoregulation of many experimental helminth infections prompted a detailed study of the cellular immune response against Fasciola hepatica in the natural bovine host. T-cell lines established from two cattle infected with F. hepatica were characterized for the expression of T-cell surface markers and proliferative responses against F. hepatica adult worm antigen. Parasite-specific T-cell lines contained a mixture of CD4+, CD8+, and gamma/delta T-cell-receptor-bearing T cells. However, cell lines containing either fewer than 10% CD8+ T cells or depleted of gamma/delta T cells proliferated vigorously against F. hepatica antigen, indicating that these T-cell subsets are not required for proliferative responses in vitro. Seventeen F. hepatica-specific CD4+ Th-cell clones were examined for cytokine expression following concanavalin A stimulation. Biological assays to measure interleukin-2 (IL-2) or IL-4, gamma interferon (IFN-gamma), and tumor necrosis factor and Northern (RNA) blot analysis to verify the expression of IL-2, IL-4, and IFN-gamma revealed that the Th-cell clones expressed a spectrum of cytokine profiles. Several Th-cell clones were identified as Th2 cells by the strong expression of IL-4 but little or no IL-2 or IFN-gamma mRNA. The majority of Th-cell clones were classified as Th0 cells by the expression of either all three cytokines or combinations of IL-2 and IL-4 or IL-4 and IFN-gamma. No Th1-cell clones were obtained. All of the Th-cell clones expressed a typical memory cell surface phenotype, characterized as CD45Rlow, and all expressed the lymph node homing receptor (L selectin). These results are the first to describe cytokine responses of F. hepatica-specific T cells obtained from infected cattle and extend our previous analysis of Th0 and Th1 cells from cattle immune to Babesia bovis (W. C. Brown, V. M. Woods, D. A. E. Dobbelaere, and K. S. Logan, Infect. Immun. 61:3273-3281, 1993) to include F. hepatica-specific Th2 cells.

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Selected References

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  1. Armour J., Dargie J. D. Immunity to Fasciola hepatica in the rat. Successful transfer of immunity by lymphoid cells and by serum. Exp Parasitol. 1974 Jun;35(3):381–388. doi: 10.1016/0014-4894(74)90044-7. [DOI] [PubMed] [Google Scholar]
  2. Brown W. C., Grab D. J. Biological and biochemical characterization of bovine interleukin 2. Studies with cloned bovine T cells. J Immunol. 1985 Nov;135(5):3184–3190. [PubMed] [Google Scholar]
  3. Brown W. C., Logan K. S. Babesia bovis: bovine helper T cell lines reactive with soluble and membrane antigens of merozoites. Exp Parasitol. 1992 Mar;74(2):188–199. doi: 10.1016/0014-4894(92)90046-d. [DOI] [PubMed] [Google Scholar]
  4. Brown W. C., Logan K. S., Wagner G. G., Tetzlaff C. L. Cell-mediated immune responses to Babesia bovis merozoite antigens in cattle following infection with tick-derived or cultured parasites. Infect Immun. 1991 Jul;59(7):2418–2426. doi: 10.1128/iai.59.7.2418-2426.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown W. C., Woods V. M., Dobbelaere D. A., Logan K. S. Heterogeneity in cytokine profiles of Babesia bovis-specific bovine CD4+ T cells clones activated in vitro. Infect Immun. 1993 Aug;61(8):3273–3281. doi: 10.1128/iai.61.8.3273-3281.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown W. C., Zhao S., Rice-Ficht A. C., Logan K. S., Woods V. M. Bovine helper T cell clones recognize five distinct epitopes on Babesia bovis merozoite antigens. Infect Immun. 1992 Oct;60(10):4364–4372. doi: 10.1128/iai.60.10.4364-4372.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brown W. C., Zhao S., Woods V. M., Tripp C. A., Tetzlaff C. L., Heussler V. T., Dobbelaere D. A., Rice-Ficht A. C. Identification of two Th1 cell epitopes on the Babesia bovis-encoded 77-kilodalton merozoite protein (Bb-1) by use of truncated recombinant fusion proteins. Infect Immun. 1993 Jan;61(1):236–244. doi: 10.1128/iai.61.1.236-244.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Capron A., Dessaint J. P., Capron M., Ouma J. H., Butterworth A. E. Immunity to schistosomes: progress toward vaccine. Science. 1987 Nov 20;238(4830):1065–1072. doi: 10.1126/science.3317823. [DOI] [PubMed] [Google Scholar]
  9. Caulada-Benedetti Z., al-Zamel F., Sher A., James S. Comparison of Th1- and Th2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae. J Immunol. 1991 Mar 1;146(5):1655–1660. [PubMed] [Google Scholar]
  10. Colina K. F., Perler F. B., Matsumura I., Meda M., Nutman T. B. The identification of an Onchocerca-specific recombinant antigen containing a T cell epitope. J Immunol. 1990 Sep 1;145(5):1551–1556. [PubMed] [Google Scholar]
  11. Corba J., Armour J., Roberts R. J., Urquhart G. M. Transfer of immunity to Fasciola hepatica infection by lymphoid cells. Res Vet Sci. 1971 May;12(3):292–295. [PubMed] [Google Scholar]
  12. Degen J. L., Neubauer M. G., Degen S. J., Seyfried C. E., Morris D. R. Regulation of protein synthesis in mitogen-activated bovine lymphocytes. Analysis of actin-specific and total mRNA accumulation and utilization. J Biol Chem. 1983 Oct 25;258(20):12153–12162. [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Doyle J. J. Acquired immunity to experimental infection with Fasciola hepatica in cattle. Res Vet Sci. 1971 Nov;12(6):527–534. [PubMed] [Google Scholar]
  16. Doyle J. J. Skin hypersensitivity reactions induced in calves by experimental infections with Fasciola hepatica. Int Arch Allergy Appl Immunol. 1973;45(5):752–758. doi: 10.1159/000231074. [DOI] [PubMed] [Google Scholar]
  17. Finkelman F. D., Pearce E. J., Urban J. F., Jr, Sher A. Regulation and biological function of helminth-induced cytokine responses. Immunol Today. 1991 Mar;12(3):A62–A66. doi: 10.1016/S0167-5699(05)80018-0. [DOI] [PubMed] [Google Scholar]
  18. Firestein G. S., Roeder W. D., Laxer J. A., Townsend K. S., Weaver C. T., Hom J. T., Linton J., Torbett B. E., Glasebrook A. L. A new murine CD4+ T cell subset with an unrestricted cytokine profile. J Immunol. 1989 Jul 15;143(2):518–525. [PubMed] [Google Scholar]
  19. Haroun E. T., Hillyer G. V. Resistance to fascioliasis--a review. Vet Parasitol. 1986 Mar;20(1-3):63–93. doi: 10.1016/0304-4017(86)90093-2. [DOI] [PubMed] [Google Scholar]
  20. Heussler V. T., Eichhorn M., Dobbelaere D. A. Cloning of a full-length cDNA encoding bovine interleukin 4 by the polymerase chain reaction. Gene. 1992 May 15;114(2):273–278. doi: 10.1016/0378-1119(92)90587-f. [DOI] [PubMed] [Google Scholar]
  21. Hillyer G. V., Haroun E. T., Hernandez A., de Galanes M. S. Acquired resistance to Fasciola hepatica in cattle using a purified adult worm antigen. Am J Trop Med Hyg. 1987 Sep;37(2):363–369. [PubMed] [Google Scholar]
  22. Howard C. J., Sopp P., Parsons K. R. L-selectin expression differentiates T cells isolated from different lymphoid tissues in cattle but does not correlate with memory. Immunology. 1992 Oct;77(2):228–234. [PMC free article] [PubMed] [Google Scholar]
  23. Howard C. J., Sopp P., Parsons K. R., McKeever D. J., Taracha E. L., Jones B. V., MacHugh N. D., Morrison W. I. Distinction of naive and memory BoCD4 lymphocytes in calves with a monoclonal antibody, CC76, to a restricted determinant of the bovine leukocyte-common antigen, CD45. Eur J Immunol. 1991 Sep;21(9):2219–2226. doi: 10.1002/eji.1830210933. [DOI] [PubMed] [Google Scholar]
  24. Hsieh C. S., Macatonia S. E., Tripp C. S., Wolf S. F., O'Garra A., Murphy K. M. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993 Apr 23;260(5107):547–549. doi: 10.1126/science.8097338. [DOI] [PubMed] [Google Scholar]
  25. James S. L., Sher A. Cell-mediated immune response to schistosomiasis. Curr Top Microbiol Immunol. 1990;155:21–31. doi: 10.1007/978-3-642-74983-4_2. [DOI] [PubMed] [Google Scholar]
  26. Ju S. T., Ruddle N. H., Strack P., Dorf M. E., DeKruyff R. H. Expression of two distinct cytolytic mechanisms among murine CD4 subsets. J Immunol. 1990 Jan 1;144(1):23–31. [PubMed] [Google Scholar]
  27. Keegan P. S., Trudgett A. Fasciola hepatica in the rat: immune responses associated with the development of resistance to infection. Parasite Immunol. 1992 Nov;14(6):657–669. doi: 10.1111/j.1365-3024.1992.tb00037.x. [DOI] [PubMed] [Google Scholar]
  28. Kelso A., Troutt A. B., Maraskovsky E., Gough N. M., Morris L., Pech M. H., Thomson J. A. Heterogeneity in lymphokine profiles of CD4+ and CD8+ T cells and clones activated in vivo and in vitro. Immunol Rev. 1991 Oct;123:85–114. doi: 10.1111/j.1600-065x.1991.tb00607.x. [DOI] [PubMed] [Google Scholar]
  29. Maggi E., Parronchi P., Manetti R., Simonelli C., Piccinni M. P., Rugiu F. S., De Carli M., Ricci M., Romagnani S. Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones. J Immunol. 1992 Apr 1;148(7):2142–2147. [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. Oldham G., Williams L. Cell mediated immunity to liver fluke antigens during experimental Fasciola hepatica infection of cattle. Parasite Immunol. 1985 Sep;7(5):503–516. doi: 10.1111/j.1365-3024.1985.tb00095.x. [DOI] [PubMed] [Google Scholar]
  33. Overton W. R. Modified histogram subtraction technique for analysis of flow cytometry data. Cytometry. 1988 Nov;9(6):619–626. doi: 10.1002/cyto.990090617. [DOI] [PubMed] [Google Scholar]
  34. Paliard X., de Waal Malefijt R., Yssel H., Blanchard D., Chrétien I., Abrams J., de Vries J., Spits H. Simultaneous production of IL-2, IL-4, and IFN-gamma by activated human CD4+ and CD8+ T cell clones. J Immunol. 1988 Aug 1;141(3):849–855. [PubMed] [Google Scholar]
  35. Rajasekariah G. R., Howell M. J. Fasciola hepatica in rats: transfer of immunity by serum and cells from infected to F. hepatica naive animals. J Parasitol. 1979 Aug;65(4):481–487. [PubMed] [Google Scholar]
  36. Reeves R., Spies A. G., Nissen M. S., Buck C. D., Weinberg A. D., Barr P. J., Magnuson N. S., Magnuson J. A. Molecular cloning of a functional bovine interleukin 2 cDNA. Proc Natl Acad Sci U S A. 1986 May;83(10):3228–3232. doi: 10.1073/pnas.83.10.3228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Reiner S. L., Wang Z. E., Hatam F., Scott P., Locksley R. M. TH1 and TH2 cell antigen receptors in experimental leishmaniasis. Science. 1993 Mar 5;259(5100):1457–1460. doi: 10.1126/science.8451641. [DOI] [PubMed] [Google Scholar]
  38. Romagnani S. Human TH1 and TH2 subsets: doubt no more. Immunol Today. 1991 Aug;12(8):256–257. doi: 10.1016/0167-5699(91)90120-I. [DOI] [PubMed] [Google Scholar]
  39. Ruddle N. H., Bergman C. M., McGrath K. M., Lingenheld E. G., Grunnet M. L., Padula S. J., Clark R. B. An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. J Exp Med. 1990 Oct 1;172(4):1193–1200. doi: 10.1084/jem.172.4.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Salmon M., Kitas G. D., Bacon P. A. Production of lymphokine mRNA by CD45R+ and CD45R- helper T cells from human peripheral blood and by human CD4+ T cell clones. J Immunol. 1989 Aug 1;143(3):907–912. [PubMed] [Google Scholar]
  41. Sexton J. L., Milner A. R., Panaccio M., Waddington J., Wijffels G., Chandler D., Thompson C., Wilson L., Spithill T. W., Mitchell G. F. Glutathione S-transferase. Novel vaccine against Fasciola hepatica infection in sheep. J Immunol. 1990 Dec 1;145(11):3905–3910. [PubMed] [Google Scholar]
  42. 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]
  43. Sher A., Gazzinelli R. T., Oswald I. P., Clerici M., Kullberg M., Pearce E. J., Berzofsky J. A., Mosmann T. R., James S. L., Morse H. C., 3rd Role of T-cell derived cytokines in the downregulation of immune responses in parasitic and retroviral infection. Immunol Rev. 1992 Jun;127:183–204. doi: 10.1111/j.1600-065x.1992.tb01414.x. [DOI] [PubMed] [Google Scholar]
  44. Stadecker M. J. The role of T-cell anergy in the immunomodulation of schistosomiasis. Parasitol Today. 1992 Jun;8(6):199–204. doi: 10.1016/0169-4758(92)90264-3. [DOI] [PubMed] [Google Scholar]
  45. Street N. E., Schumacher J. H., Fong T. A., Bass H., Fiorentino D. F., Leverah J. A., Mosmann T. R. Heterogeneity of mouse helper T cells. Evidence from bulk cultures and limiting dilution cloning for precursors of Th1 and Th2 cells. J Immunol. 1990 Mar 1;144(5):1629–1639. [PubMed] [Google Scholar]
  46. Swain S. L., Bradley L. M., Croft M., Tonkonogy S., Atkins G., Weinberg A. D., Duncan D. D., Hedrick S. M., Dutton R. W., Huston G. Helper T-cell subsets: phenotype, function and the role of lymphokines in regulating their development. Immunol Rev. 1991 Oct;123:115–144. doi: 10.1111/j.1600-065x.1991.tb00608.x. [DOI] [PubMed] [Google Scholar]
  47. Umetsu D. T., Jabara H. H., DeKruyff R. H., Abbas A. K., Abrams J. S., Geha R. S. Functional heterogeneity among human inducer T cell clones. J Immunol. 1988 Jun 15;140(12):4211–4216. [PubMed] [Google Scholar]
  48. Yssel H., Johnson K. E., Schneider P. V., Wideman J., Terr A., Kastelein R., De Vries J. E. T cell activation-inducing epitopes of the house dust mite allergen Der p I. Proliferation and lymphokine production patterns by Der p I-specific CD4+ T cell clones. J Immunol. 1992 Feb 1;148(3):738–745. [PubMed] [Google Scholar]

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