Abstract
The fundamental basis of immunity to infectious diseases involves a complex interplay between humoral and cell-mediated immune responses against antigens on the foreign pathogen. Humoral immunity, either in the form of local IgA antibodies at the mucosal site of infection or neutralizing antibodies in the serum, provides the first line of defense against invading microorganisms. However, cellular immunity, mediated by T-cells, also plays a major role in protection against foreign pathogens. CD8+ cytotoxic T-lymphocytes (CTLs) kill target cells infected with viruses or bacteria, whereas CD4+ T-helper (Th) cells provide help for B-cells in antibody production and secrete a range of cytokines that are involved in a variety of immunoregulatory functions or have a direct effect on invading microorganisms (1–3). CD4+ T-cells can be divided into subpopulations on the basis of their function and cytokine secretion (4). Thl cells secrete interleukin 2 (IL-2), γ-interferon (IFN-γ), and tumor necrosis factor-β (TNF-β) and are involved in delayed-type hypersensitivity and inflammatory responses, and display CTL activity in vitro. A key function of this CD4+ Thl population in the immunological defense mechanism in vivo appears to be the activation of macrophages, which are stimulated to take up and kill invading microorganisms. In contrast, Th2-cells, which secrete IL-4, lL-5, IL-6, and IL-10, are considered to be the true helper T-cells; their secreted cytokines play a crucial role in immunoglobulin (Ig) class switching and B-cell differentiation, in particular for IgE, IgA, and IgG1 antibody production (5).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Mills, K. H. G. (1989) Recognition of foreign antigen by T cells and their role in immune protection. Curr. Opin. Infect. Dis. 2, 804–814.
Jankovic, D., Liu, Z., and Gause, W.C. (2001) Th1-and Th2-cell commitment during infectious diseases: asymmetry in divergent pathways. Trends Immunol. 22, 450–457.
Janeway, C.A. (2001) How the immune system works to protect the host from infection: a personal view. Proc. Natl. Acad. Sci. USA 98, 6461–7268.
Mosmann, T. R. and Coffman, R. L. (1989) Thl and Th2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 7, 145–173.
Abbas, A. K., Murphy, K. M., and Sher, A. (1996) Functional diversity of helper T lymphocytes. Nature 383, 787–793.
Mahon, B. P., Katrak, K., Nomoto, A., Macadam, A., Minor, P. D., and Mills, K. H. G. (1995) Poliovirus-specific Thl clones with cytotoxic and helper activity mediate protective humoral immunity against a lethal poliovirus infection in a transgenic mouse model. J. Exp. Med. 181, 1285–1292.
Groux, H., O’Garra, A., Bigler, M., Rouleau, M., Antonenko, S., De Vries, J. E., and Roncarolo, M. G. (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737–742.
Chen, Y., Kuchroo, V. K., Inobe, I., Hafler, D. A., and Weiner, H. L. (1994). Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 265, 1237–1240.
McGuirk, P., McCann, C., and Mills, K. H. G. (2002) Pathogen-specific T regulatory 1 (Tr1) cells induced in the respiratory tract by a bacterial molecule that stimulates IL-10 production by dendritic cells: a novel strategy for evasion of protective Th1 responses against Bordetella pertussis. J. Exp. Med. 195, 221–231.
Schwartz, R. H. (1985) T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu. Rev. Immunol. 3, 237–261.
Zinkernagel, R. M. and Doherty, P. C. (1979) MHC restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T cell restriction specificity, function and responsiveness. Adv. Immunol. 27, 51–77.
Mills, K. H. G. (1986) Processing of viral antigens and presentation to class II-restricted T cells. Immunol. Today 7, 260–263.
Townsend, A. R. M., Gotch, F. M., and Davey, J. (1985) Cytotoxic T-cells recognise fragments of the influenza nucleoprotein. Cell 42, 457–467.
Watts, C. and Powis, S. (1999) Pathways of antigen processing and presentation. Rev. Immunogenet. 1, 60–74.
Morrison, L. A., Lukacher, A. E., Braciale, V. L., Fan, D. P., and Braciale, T. J. (1986) Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytotoxic T lymphocyte clones. J. Exp. Med. 163, 903–921.
Raychaudhuri, S. and Morrow, W. J. W. (1993) Can soluble antigen induce CD8+ cytotoxic T cell responses? A paradox revisited. Immunol. Today 14, 344–348.
Mills, K. H. G., Skehel, J. J., and Thomas, D. B. (1986) Conformational dependent recognition of influenza virus haemagglutinin by murine T-helper clones. Eur. J. Immunol. 16, 276–280.
Mills, K. H. G., Burt, D. S., Skehel, J. J., and Thomas, D. B. (1988) Fine specificity of murine class-II-restricted T-cell clones for synthetic peptides of influenza virus haemaglutinin: heterogeneity of antigen interaction with the T-cell and the Ia molecule. J. Immunol. 140, 4083–4090.
Czerkinsky, C. Anjuere, F., McGhee, J. R., George-Chandy, A., Holmgren, J., Kieny, M. P., et al. (1999) Mucosal immunity and tolerance: relevance to vaccine development. Immunol. Rev. 170, 197–222.
Ryan, E. R., Daly, L., and Mills K. H. G. (2001) Immunomodulators and delivery systems for vaccination by mucosal routes. Trends Biotechnol. 19, 293–304.
Moser, M. and Murphy, K. M. (2000) Dendritic cell regulation of TH1-TH2 development. Nat. Immunol. 1, 199–205.
Whelan, M., Harnett, M. M., Houston, K. M., Patel, V., Harnett, M., and Rigley, K. P. (2000) A filarial nematode-secreted product signals dendritic cells to acquire a phenotype that drives development of Th2 cells. J. Immunol. 164, 6453–6460.
Aguado, T., Engers, H., Pang, T., and Pink, R. (1999) Novel adjuvants in clinical testing November 2–4, 1998, Fondation Merieux, Annecy, France: a meeting sponsored by the World Health Organization. Vaccine 17, 2321–2328.
Allison, A. C. and Byars, N. E. (1986) An adjuvant formulation that selectively elicits the formation of antibodies of protective isotypes and of cell-mediated immunity. J. Immunol. Methods 95, 157–168.
Smith R. E., Donachie, A. M., and Mowat, A. M. (1998) Immune stimulating complexes as mucosal vaccines. Immunol. Cell Biol. 76, 263–269.
Conway, M., Madrigal, L., McClean, S., Brayden, D. J., and Mills, K. H. G. (2001) Protection against Bordetella pertussis infection following parenteral or oral immunization with antigens entrapped in biodegradable polymers: effect of formulation and route of immunization on induction of Th1 and Th2 cells. Vaccine 19, 1940–1950.
Mills, K. H. G., Kitchin, P. A., Mahon, B. P., Barnard, A. L., Adams, S. E., Kingsman, S. M., et al. (1990) HIV p24-specific T cell clones from immunized primates recognize highly conserved regions of HIV-1. J. Immunol. 144, 1677–1683.
Ribi, E. and Cantrell, J. (1985) A new immunomodulator with potential clinical applications: monophosphoryl lipid A, a detoxified endotoxin. Clinical Immunol. News 6, 33–36.
Marinaro, M., Staats, H. F., Hiroi, T., Jackson, R. J., Coste, M., Boyaka, P. N., et al. (1995) Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4. J. Immunol. 155, 4621–4629.
Ryan, E. J., McNeela, E., Murphy, G., Stewart, H., O’Hagan, D., Pizza, M., et al. (1999) Mutants of Escherichia coli heat labile toxin act as effective mucosal adjuvants for nasal delivery of an acellular pertussis vaccine: differential effects of the nontoxic AB complex and enzyme activity on Th1 and Th2 cells. Infect. Immun. 67, 6270–6280.
Ogra, P. L. and Garofalo, R. (1990) Secretory antibody response to viral vaccines. Prog. Med. Virol. 37, 156–189.
Mills, K. H. G., Cosgrove, C., McNeela, E. A., Sexton, A., Giemza, R., Jabbal-Gill, I., et al. (2003) Protective diptheria immunity induced in healthy volunteers by unilateral prime-boost intranasal immunization associated with restricted ispilateral mucosal secretory IgA. Infect. Immun. 71, 726–732.
Mills, K. H. G. (2000) Murine T cell culture, in Lymphocytes—A Practical Approach. (Rowland Jones, S. and McMichael, A., eds.) IRL Press, Oxford, pp. 95–134.
Mills, K. H. G. (1986) An indirect rosette technique for the identification and separation of lymphocyte subpopulations by monoclonal antibodies, in Immunological Techniques, Methods in Enzymology, vol. 121. Immunochemical Techniques (Langone, J. J. and van Vunakis, H., eds.), Academic Press, Boca Raton, FL, pp. 726–737.
Plebanski, M. (2000) Preparation of lymphocyte and identification of lymphocyte subpopulations, in Lymphocytes—A Practical Approach (Rowland Jones, S. and McMichael, A., eds.) IRL Press, Oxford, pp 1–26.
Carmichael, A. (2000) Limiting dilution-analysis for the quantitation of antigen-specific T cells, in Lymphocytes—A Practical Approach (Rowland Jones, S. and McMichael, A., eds.) IRL Press, Oxford. Pp. 179–196.
Ogg, G. S. (2000) HLA-peptide tetrameric complexes, in Lymphocytes—A Practical Approach (Rowland Jones, S. and McMichael, A., eds.) IRL Press, Oxford. Pp. 197–208.
Mills, K. H. G., Skehel, J. J., and Thomas, D. B. (1986) Extensive diversity in the recognition of influenza virus hemagglutinin by murine T helper clones. J. Exp. Med. 163, 1477–1490.
Dresser, D. (1986) Immunization of experimental animals, in Handbook of Experimental Immunology, 4th ed. (Weir, M., ed.), Blackwell Scientific, Oxford, pp. 8.1–8.21.
Katrak, K., Mahon, B. P., Jones, W., Brautigam, S., and Mills, K. H. G. (1992) Preparative separation of foreign antigens for highly efficient presentation to T cells in vitro. J. Immunol. Methods 156, 247–254.
Melby, P. C., Damsel, B. J., and Tryon, V. V. (1993) Quantative measurement of human cytokine gene expression by polymerase chain reaction. J. Immunol. Methods 159, 235–243.
Jung, T., Schauer, U., Heusser, C., Neumann, C., and Rieger, C. (1993) Detection of intracellular cytokines by flow cytometry. J. Immunol. Methods 159, 197–207.
Thorpe, R., Wadhwa, M., Bird, C. R., and Mire-Sluis, A. R. (1992) Detection and measurement of cytokines. Blood Rev. 6, 133–148.
Knight, S. (1987) Lymphocyte proliferation assays, in Lymphocytes—A Practical Approach (Klaus, G. G. B., ed.), IRL, Oxford, pp. 189–208.
Moore, A., McCarthy, L., and Mills, K. H. G. (1999) The adjuvant combination monophosphoryl lipid A and QS21 switches T cell responses induced with a recombinant HIV protein from Th2 to Th1. Vaccine 17, 2517–2527.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Mills, K.H.G. (2003). Induction and Detection of T-Cell Responses. In: Robinson, A., Hudson, M.J., Cranage, M.P. (eds) Vaccine Protocols. Methods in Molecular Medicine™, vol 87. Humana Press. https://doi.org/10.1385/1-59259-399-2:255
Download citation
DOI: https://doi.org/10.1385/1-59259-399-2:255
Publisher Name: Humana Press
Print ISBN: 978-1-58829-140-0
Online ISBN: 978-1-59259-399-6
eBook Packages: Springer Protocols