Abstract
The roles of CD4+ and CD8+ T cells in genetically determined resistance of sheep to Haemonchus contortus (a natural host-parasite relationship) was investigated by selectively depleting genetically resistant merino lambs of their CD4+ or CD8+ T cells by treatment with mouse monoclonal antibody (mAb) specific for the appropriate determinant before and during challenge infection. Administration of anti-CD4 mAb to genetically resistant lambs completely abrogated their expression of genetic resistance as indicated by significantly higher faecal egg output and worm burdens found in the CD4+ T-cell-depleted lambs compared with those of controls. Host responses associated with resistance to H. contortus including mucosal mast cell hyperplasia and tissue eosinophilia were also significantly suppressed in CD4-depleted lambs. The development of anamnestic anti-parasite antibody responses were also significantly inhibited by anti-CD4 mAb. Furthermore, anti-CD4 mAb abolished differences in host responses between genetically resistant and random-bred (susceptible) lambs. In contrast, depletion of CD8+ T cells had no effect on genetic resistance; faecal egg output, worm counts, mast cells and eosinophil responses in CD8-depleted lambs were not significantly different from those in controls. Together, these results suggest that CD4+ T cells play a pivotal role in mediating genetic resistance to H. contortus, and in the generation of mucosal mast cell hyperplasia, tissue eosinophilia and anti-Haemonchus antibody. CD8+ T cells appear to play no protective role. The possible mechanisms by which CD4+ T cells might mediate anti-parasite resistance are discussed.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abe T., Nawa Y. Worm expulsion and mucosal mast cell response induced by repetitive IL-3 administration in Strongyloides ratti-infected nude mice. Immunology. 1988 Feb;63(2):181–185. [PMC free article] [PubMed] [Google Scholar]
- Abu-Ghazaleh R. I., Fujisawa T., Mestecky J., Kyle R. A., Gleich G. J. IgA-induced eosinophil degranulation. J Immunol. 1989 Apr 1;142(7):2393–2400. [PubMed] [Google Scholar]
- Albers G. A., Gray G. D., Piper L. R., Barker J. S., Le Jambre L. F., Barger I. A. The genetics of resistance and resilience to Haemonchus contortus infection in young merino sheep. Int J Parasitol. 1987 Oct;17(7):1355–1363. doi: 10.1016/0020-7519(87)90103-2. [DOI] [PubMed] [Google Scholar]
- Askenase P. W. Role of basophils, mast cells, and vasoamines in hypersensitivity reactions with a delayed time course. Prog Allergy. 1977;23:199–320. [PubMed] [Google Scholar]
- Butterworth A. E. Cell-mediated damage to helminths. Adv Parasitol. 1984;23:143–235. doi: 10.1016/s0065-308x(08)60287-0. [DOI] [PubMed] [Google Scholar]
- 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]
- Dineen J. K., Gregg P., Lascelles A. K. The response of lambs to vaccination at weaning with irradiated Trichostrongylus colubriformis larvae: segregation into 'responders' and 'non-responders'. Int J Parasitol. 1978 Feb;8(1):59–63. doi: 10.1016/0020-7519(78)90052-8. [DOI] [PubMed] [Google Scholar]
- Emery D. L., Wagland B. M. Vaccines against gastrointestinal nematode parasites of ruminants. Parasitol Today. 1991 Dec;7(12):347–349. doi: 10.1016/0169-4758(91)90217-c. [DOI] [PubMed] [Google Scholar]
- Gill H. S. Genetic control of acquired resistance to haemonchosis in Merino lambs. Parasite Immunol. 1991 Nov;13(6):617–628. doi: 10.1111/j.1365-3024.1991.tb00557.x. [DOI] [PubMed] [Google Scholar]
- Gill H. S., Watson D. L., Brandon M. R. In vivo inhibition by a monoclonal antibody to CD4+ T cells of humoral and cellular immunity in sheep. Immunology. 1992 Sep;77(1):38–42. [PMC free article] [PubMed] [Google Scholar]
- Gordon J. R., Burd P. R., Galli S. J. Mast cells as a source of multifunctional cytokines. Immunol Today. 1990 Dec;11(12):458–464. doi: 10.1016/0167-5699(90)90176-a. [DOI] [PubMed] [Google Scholar]
- Grencis R. K., Riedlinger J., Wakelin D. L3T4-positive T lymphoblasts are responsible for transfer of immunity to Trichinella spiralis in mice. Immunology. 1985 Oct;56(2):213–218. [PMC free article] [PubMed] [Google Scholar]
- Huntley J. F., Newlands G., Miller H. R. The isolation and characterization of globule leucocytes: their derivation from mucosal mast cells in parasitized sheep. Parasite Immunol. 1984 Jul;6(4):371–390. doi: 10.1111/j.1365-3024.1984.tb00809.x. [DOI] [PubMed] [Google Scholar]
- Katona I. M., Urban J. F., Jr, Finkelman F. D. The role of L3T4+ and Lyt-2+ T cells in the IgE response and immunity to Nippostrongylus brasiliensis. J Immunol. 1988 May 1;140(9):3206–3211. [PubMed] [Google Scholar]
- Madden K. B., Urban J. F., Jr, Ziltener H. J., Schrader J. W., Finkelman F. D., Katona I. M. Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis. J Immunol. 1991 Aug 15;147(4):1387–1391. [PubMed] [Google Scholar]
- Maddox J. F., Mackay C. R., Brandon M. R. Surface antigens, SBU-T4 and SBU-T8, of sheep T lymphocyte subsets defined by monoclonal antibodies. Immunology. 1985 Aug;55(4):739–748. [PMC free article] [PubMed] [Google Scholar]
- Miller H. R. The protective mucosal response against gastrointestinal nematodes in ruminants and laboratory animals. Vet Immunol Immunopathol. 1984 May;6(1-2):167–259. doi: 10.1016/0165-2427(84)90051-5. [DOI] [PubMed] [Google Scholar]
- Murray P. K. Prospects for molecular vaccines in veterinary parasitology. Vet Parasitol. 1987 Jul;25(2):121–133. doi: 10.1016/0304-4017(87)90099-9. [DOI] [PubMed] [Google Scholar]
- Presson B. L., Gray G. D., Burgess S. K. The effect of immunosuppression with dexamethasone on Haemonchus contortus infections in genetically resistant merino sheep. Parasite Immunol. 1988 Nov;10(6):675–680. doi: 10.1111/j.1365-3024.1988.tb00253.x. [DOI] [PubMed] [Google Scholar]
- Rothwell T. L. Immune expulsion of parasitic nematodes from the alimentary tract. Int J Parasitol. 1989 Apr;19(2):139–168. doi: 10.1016/0020-7519(89)90003-9. [DOI] [PubMed] [Google Scholar]
- Sher A., Coffman R. L., Hieny S., Cheever A. W. Ablation of eosinophil and IgE responses with anti-IL-5 or anti-IL-4 antibodies fails to affect immunity against Schistosoma mansoni in the mouse. J Immunol. 1990 Dec 1;145(11):3911–3916. [PubMed] [Google Scholar]
- Smith W. D., Jackson F., Jackson E., Graham R., Williams J., Willadsen S. M., Fehilly C. B. Transfer of immunity to Ostertagia circumcincta and IgA memory between identical sheep by lymphocytes collected from gastric lymph. Res Vet Sci. 1986 Nov;41(3):300–306. [PubMed] [Google Scholar]
- Smith W. D., Jackson F., Jackson E., Williams J. Age immunity to Ostertagia circumcincta: comparison of the local immune responses of 4 1/2- and 10-month-old lambs. J Comp Pathol. 1985 Apr;95(2):235–245. doi: 10.1016/0021-9975(85)90010-6. [DOI] [PubMed] [Google Scholar]
- Smith W. D., Jackson F., Jackson E., Williams J., Willadsen S. M., Fehilly C. B. Resistance to Haemonchus contortus transferred between genetically histocompatible sheep by immune lymphocytes. Res Vet Sci. 1984 Sep;37(2):199–204. [PubMed] [Google Scholar]
- Urban J. F., Jr, Katona I. M., Finkelman F. D. Heligmosomoides polygyrus: CD4+ but not CD8+ T cells regulate the IgE response and protective immunity in mice. Exp Parasitol. 1991 Nov;73(4):500–511. doi: 10.1016/0014-4894(91)90074-7. [DOI] [PubMed] [Google Scholar]
- Urban J. F., Jr, Katona I. M., Paul W. E., Finkelman F. D. Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5513–5517. doi: 10.1073/pnas.88.13.5513. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waller P. J. Anthelmintic resistance and the future for roundworm control. Vet Parasitol. 1987 Jul;25(2):177–191. doi: 10.1016/0304-4017(87)90103-8. [DOI] [PubMed] [Google Scholar]
- Weller P. F., Goetzl E. J. The regulatory and effector roles of eosinophils. Adv Immunol. 1979;27:339–371. doi: 10.1016/s0065-2776(08)60264-3. [DOI] [PubMed] [Google Scholar]