Hostname: page-component-7479d7b7d-c9gpj Total loading time: 0 Render date: 2024-07-11T00:04:34.608Z Has data issue: false hasContentIssue false

Dynamic interaction between CD4+ T cells and parasitic helminths: mathematical models of heterogeneity in outcome

Published online by Cambridge University Press:  06 April 2009

A. N. Schweitzer
Affiliation:
Wellcome Research Centre for Parasitic Infections, Department of Biology, Imperial College, London SW7 2BB
R. M. Anderson
Affiliation:
Wellcome Research Centre for Parasitic Infections, Department of Biology, Imperial College, London SW7 2BB

Summary

Potential mechanisms of immunoregulation have been investigated for the capacity to generate heterogeneity in the outcome of infection with helminth parasites. We have developed a mathematical model of the interaction between T cell and parasite populations, based on the assumption that activation of a Th1 CD4+ T cell response is required for host resistance. Antigen dose-dependent inhibition of Th1 cell proliferation generates heterogeneity in the outcome of host response to infection, with relatively low levels of exposure inducing resistance, and high levels of exposure associated with host susceptibility. Heterogeneity is additionally predicted in the duration of infection before individuals of the resistant class clear infection, with infection becoming more prolonged as the level of exposure rises. Similar categories of response are predicted if an alternative regulatory mechanism, that of interferon γ-regulated control of Th1 cell differentiation, is substituted into the model. However, the relationship between level of exposure and duration of infection is reversed. Results are discussed in the context of how these simple models of parasite–immune system interactions might be used to make predictions concerning specific examples of parasitic infection.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1992

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Anderson, R. M. (1978). The regulation of host population growth by parasite species. Parasitology 76, 119–57.CrossRefGoogle Scholar
Anderson, R. M. (1991). Populations and infectious diseases: ecology or epidemiology? Journal of Animal Ecology 60, 150.CrossRefGoogle Scholar
Anderson, R. M. & Gordon, D. M. (1982). Processes influencing the distribution of parasite numbers within host populations with special emphasis on parasite-induced host mortalities. Parasitology 85, 373–98.CrossRefGoogle ScholarPubMed
Borel, Y., Fauconnet, M. & Miescher, P. A. (1966). Selective suppression of delayed hypersensitivity by the induction of immunologic tolerance. Journal of Experimental Medicine 123, 585–98.CrossRefGoogle ScholarPubMed
Bradley, J. E., Helm, R., Lahaise, M. & Maizels, R. M. (1991). cDNA clones of Onchocerca volvulus low molecular weight antigens provide immunologically specific diagnostic probes. Molecular and Biochemical Parasitology 46, 219–28.CrossRefGoogle ScholarPubMed
Bundy, D. A. P., Grenfell, B. T. & Rajagopalan, P. K. (1991 a). In Immunoparasitology Today (ed. Ash, C., Gallagher, R. B.), pp. A71–A75. Cambridge: Elsevier Trends Journals.Google Scholar
Bundy, D. A. P., Lillywhite, J. E., Didier, J. M., Simmons, I. & Bianco, A. E. (1991 b). Age-dependency of infection status and serum antibody levels in human whipworm (Trichuris trichiura) infection. Parasite Immunology 13, 629–38.CrossRefGoogle ScholarPubMed
Butterworth, A. E. & Hagan, P. (1987). Immunity in human schistosomiasis. Parasitology Today 3, 1116.CrossRefGoogle ScholarPubMed
Carman, J. A., Pond, L., Nashold, F., Wassom, D. L. & Hayes, C. E. (1992). Immunity to Trichinella spiralis infection in vitamin A-deficient mice. Journal of Experimental Medicine 175, 111–20.CrossRefGoogle ScholarPubMed
Chang, T-L., Shea, C. M., Urioste, S., Thompson, R. C., Boom, W. H. & Abbas, A. K. (1990). 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. Journal of Immunology 145, 2803–8.CrossRefGoogle ScholarPubMed
Cherwinski, H. M., Schumacher, J. H., Brown, K. D. & Mosmann, T. R. (1987). Two types of mouse helper T cell clone. III Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridisation, functionally monospecific bioassays, and monoclonal antibodies. Journal of Experimental Medicine 166, 1229–44.CrossRefGoogle ScholarPubMed
Crofton, H. D. (1971). A quantitative approach to parasitism. Parasitology 62, 179–94.CrossRefGoogle Scholar
Else, K. J. & Grensis, R. K. (1991). Cellular immune responses to the murine nematode parasite Trichuris muris. I Differential cytokine production during acute or chronic infection. Immunology 72, 508–13.Google ScholarPubMed
Fernandez-Botran, R., Sanders, V. M., Mosmann, T. R. & Vitetta, E. S. (1988). Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells. Journal of Experimental Medicine 168, 543–58.CrossRefGoogle ScholarPubMed
Finkelman, F. D., Pearce, E. J., Urban, J. F. & Sher, A. (1991). In Immunoparasitology Today (ed. Ash, C. & Gallagher, R. B.), pp. A62–A66. Cambridge: Elsevier Trends Journals.Google Scholar
Fiorentino, D. F., Bond, M. W. & Mosmann, T. R. (1989). Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. Journal of Experimental Medicine 170, 2081–95.CrossRefGoogle Scholar
Fletcher, C., Birch, D. W., Samad, R. & Denham, D. A. (1986). Brugia pahangi infections in cats: antibody responses which correlate with the change from the microfilaraemic to the amicrofilaraemic state. Parasite Immunology 8, 345–57.CrossRefGoogle Scholar
Gajewski, T. F. & Fitch, F. W. (1988). Anti-proliferative effect of IFN-γ in immune regulation. I. IFN-γ inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. Journal of Immunology 140, 4245–52.CrossRefGoogle Scholar
Gajewski, T. F., Schell, S. R. & Fitch, F. W. (1990). Evidence implicating utilisation of different T cell receptor-associated signalling pathways by Th1 and Th2 clones. Journal of Immunology 144, 4110–20.CrossRefGoogle ScholarPubMed
Gajewski, T. F., Schell, S. R., Nau, G. & Fitch, F. W. (1989). Regulation of T-cell activation: differences among T-cell subsets. Immunological Reviews 111, 79110.CrossRefGoogle ScholarPubMed
Hagan, P., Blumenthal, U. J., Dunn, D., Simpson, A. J. G. & Wilkins, H. A. (1991). Human IgGE, IgG4 and resistance to reinfection with Schistosoma haemotobium. Nature, London 349, 243–5.CrossRefGoogle Scholar
Haswell-Elkins, M. R., Elkins, D. B. & Anderson, R. M. (1987). Evidence for predisposition in humans to infection with Ascaris hookworm, Enterobius and Trichuris in a South Indian fishing community. Parasitology 95, 323–38.CrossRefGoogle Scholar
Keymer, A. E. & Anderson, R. M. (1979). The dynamics of infection of Tribolium confusum by Hymenolepis diminuta: the influence of infective-stage density and spatial distribution. Parasitology 79, 195207.CrossRefGoogle ScholarPubMed
Kurniawan, L., Basundari, E., Fuhrman, J. A., Turner, H., Purtoma, H. & Piessens, W. F. (1990). Differential recognition of microfilarial antigens by sera from immigrants into an area endemic for brugian filariasis. Parasite Immunology 12, 213–28.CrossRefGoogle ScholarPubMed
Lamb, J. R., Skidmore, B. J., Green, N., Chiller, J. M. & Feldmann, M. (1983). Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin. Journal of Experimental Medicine 157, 1434–47.CrossRefGoogle ScholarPubMed
Liew, F. Y., Yang, D. M., Severn, A. & Cox, F. E. (1991). TNF-α reverses the disease-exacerbating effect of subcutaneous immunisation against murine cutaneous leishmaniasis. Immunology 74, 304–9.Google ScholarPubMed
Locksley, R. M. & Scott, P. (1991). In Immunoparasitology Today (ed. Ash, C. & Gallagher, R. B.), pp. A58–A61. Cambridge: Elsevier Trends Journals.Google Scholar
Loewi, G., Holborow, E. J. & Temple, A. (1966). Inhibition of delayed hypersensitivity by pre-immunisation without complete adjuvant. Immunology 10, 339–47.Google Scholar
Maizels, R. M. & Lawrence, R. A. (1991). Immunological tolerance: the key feature in human filariasis? Parasitology Today 7, 271–6.CrossRefGoogle ScholarPubMed
Matis, L. A., Jones, P. P., Murphy, D. B., Hedrick, S. M., Lerner, E. A., Janeway, C. A. Jr, Mcnicholas, J. M. & Schwartz, R. H. (1982). Immune response gene function correlates with the expression of an Ia antigen. II A quantitative deficiency in Ae:Eα complex expression causes a corresponding defect in antigen-presenting cell function. Journal of Experimental Medicine 155, 508–23.CrossRefGoogle Scholar
Matis, L. A., Glimcher, L. H., Paul, W. E. & Schwartz, R. H. (1983). Magnitude of response of histocompatibility-restricted T-cell clones is a function of the product of the concentrations of antigen and Ia molecules. Journal of Experimental Medicine 80, 6019–23.Google ScholarPubMed
Moore, K. W., Vieira, P., Fiorentino, D. F., Trounstine, M. L., Khan, T. A. & Mosmann, T. M. (1990). Homology of cytokine synthesis inhibitory factor (IL-10) to the epstein-barr virus gene BCRFI. Science 248, 1230–4.CrossRefGoogle Scholar
Mosmann, T. R., Cherwinski, H., Bond, M. W., Gieldin, M. A. & Coffman, R. L. (1986). Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. Journal of Immunology 136, 2348–57.CrossRefGoogle ScholarPubMed
Mosmann, T. R. & Moore, K. W. (1991). In Immunoparasitology Today (ed. Ash, C. & Gallagher, R. B.), pp. A49–A53. Cambridge: Elsevier Trends Journals.Google Scholar
Mueller, D. L., Jenkins, M. K. & Schwartz, R. H. (1989). Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annual Reviews of Immunology 7, 445–80.CrossRefGoogle ScholarPubMed
Munoz, E., Zubiaga, A. M., Merrow, M., Sauter, N. P. & Huber, B. T. (1990). Cholera toxin discriminates between T helper 1 and 2 cells in T cell receptor-mediated activation: role of cAMP in T cell proliferation. Journal of Experimental Medicine 172, 95103.CrossRefGoogle Scholar
Parish, C. J. & Liew, F. Y. (1972). Immune response to chemically modified flagellin. III Enhanced cell-mediated immunity during high and low zone antibody tolerance to flagellin. Journal of Experimental Medicine 135, 298311.CrossRefGoogle Scholar
Pearce, E. J., Caspar, P., Grzych, J-M., Lewis, F. A. & Sher, A. (1991). Down-regulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. Journal of Experimental Medicine 173, 159–66.CrossRefGoogle ScholarPubMed
PelemanR., WU R., WU, Fargeas., C. , C. & Delespesse, G. (1989) Recombinant interleukin 4 suppresses the production of interferon γ by human mononuclear cells. Journal of Experimental Medicine 170, 1751–6.CrossRefGoogle ScholarPubMed
Powers, G. D., Abbas, A. K. & Miller, R. A. (1988). Frequencies of IL-2- and IL-4-secreting T cells in naive and antigen-stimulated lymphocyte populations. Journal of Immunology 140, 3352–7.CrossRefGoogle ScholarPubMed
Pritchard, D. I., Ali, N. M. H. & Behnke, J. M. (1984). Analysis of the mechanism of immunosuppression following heterologous antigenic stimulation during concurrent infection with Nematospiroides dubius. Immunology 51, 633–42.Google ScholarPubMed
Romagnani, S. (1991). Human Th1 and Th2 subsets: doubt no more. Immunology Today 12, 256–7.CrossRefGoogle ScholarPubMed
Schad, G. A. & Anderson, R. M. (1985). Predisposition to hookworm infection in man. Science 228, 1537–40.CrossRefGoogle Scholar
Schweitzer, N. & Anderson, R. (1991). In Immunoparasitology Today (ed. Ash, C. & Gallagher, R. B.), pp. A76–A81. Cambridge: Elsevier Trends Journals.Google Scholar
Schweitzer, A. N. & Anderson, R. M. (1992). The regulation of immunological responses to parasitic infections and the development of tolerance. Proceedings of the Royal Society, B247, 107–12.Google ScholarPubMed
Schweitzer, A. N., Swinton, J. & Anderson, R. M. (1992). Complexity in outcome in mouse leishmaniasis: a model for the dynamics of the Th1 response. In Theoretical and Experimental Insights into Immunity (ed. Perelson, A. S., Weisbuch, G. & Coutinho, A.), pp. 000–000. Berlin: Springer-Verlag.Google Scholar
Scott, P. (1991). IFNγ modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. Journal of Immunology 147, 3149–55.CrossRefGoogle Scholar
Scott, P., Pearce, E., Cheever, A. W., Coffman, R. L. & Sher, A. (1989). Role of cytokines and CD4+ T cell subsets in the regulation of parasite immunity and disease. Immunological Reviews 112, 161–82.CrossRefGoogle ScholarPubMed
Sher, A. & Colley, D. G. (1989). Immunoparasitology. In Fundamental Immunology (ed. Paul, W. E.), pp. 957984. New York: Raven Press.Google Scholar
Sher, A., Coffman, R. L., Hieny, S. & Cheever, A. W. (1990). Ablation of eosinophils and IgE responses with anti-IL-5 or anti-IL-4 antibodies fails to affect immunity against Schistosoma mansoni in the mouse. Journal of Immunology 145, 3911–16.CrossRefGoogle ScholarPubMed
Street, N. E., Schumacher, J. H., Fong, A. T., Bass, H., Fiorentino, D. F., Leverah, J. A. & Mosmann, T. R. (1990). Heterogeneity of mouse helper T cells. Evidence from bulk cultures and limiting dilution cloning for precursors of Th1 and Th2 cells. Journal of Immunology 144, 1629–39.CrossRefGoogle ScholarPubMed
Suzuki, G., Kawase, Y., Koyasu, S., Yahara, I., Kobayashi, Y. & Schwartz, R. H. (1988). Antigen-induced suppression of the proliferative response of T cell clones. Journal of Immunology 140, 1359–65.CrossRefGoogle ScholarPubMed
Swain, S. L., Mckenzie, D. T., Weinberg, A. D. & Hancock, W. (1988). Characterisation of T helper 1 and 2 cell subsets in normal mice. Helper T cells responsible for IL-4 and IL-5 production develop into lymphokine-secreting cells. Journal of Immunology 141, 3445–55.CrossRefGoogle ScholarPubMed
Toribio, M. L., Gutierrez-Ramos, J. C., Pezzi, L., Marcos, M. A. R. & Martinez, A. (1989). Interleukin-2-dependent autocrine proliferation in T-cell development. Nature, London 342, 82–5.CrossRefGoogle ScholarPubMed
Wakelin, D. M. (1984). Immunity to Parasites. London: Arnold.Google Scholar
Ward, D. J., Nutman, T. B., Zea-Flores, G., Portecarrero, C., Lujan, A. & Ottesen, E. A. (1988). Onchocerciasis and immunity in humans: enhanced T cell responsiveness to parasite antigen in putatively immune individuals. Journal of Infectious Disease 157, 536–43.CrossRefGoogle ScholarPubMed
Wassom, D. L., Dougherty, D. A., Krco, C. J. & David, C. S. (1984). H-2 controlled dose-dependent suppression of the response that expels adult Trichinella spiralis from the small intestine of mice. Immunology 53, 811–18.Google ScholarPubMed