Abstract
Differentiated CD4+T-cells produce a restricted set of cytokines, allowing their subdivision into two discrete populations: T-helper 1 (Th1), characterized by secretion of interleukin 2 (IL-2) and interferon γ (IFN-γ); and Th2, selectively producing IL-4, IL-5, and IL-10 (1). Polarized subsets of antigen(Ag)- specific CD4+Th1 and Th2 cells can be induced in vivo by Ag priming, and their development is primarily influenced by the cytokine milieu during the initial phase of the immune response. Among cytokines, decisive roles are played by IL-12 and IL-4, driving T-cell responses toward the Th1 or Th2 phenotype, respectively (2, 3). The polarization in Th1 and Th2 cells is also influenced by several other factors, including non-major histocompatibility complex (MHC) genetic polymorphism (4-6; see Note 1), ligand-T-cell receptor (TCR) interaction (7,8), Ag dose (9,10), and mode of Ag administration (11; see Note 2 ).
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References
Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A., and Coffmann, R. L. (1986) Two types of murine helper T cell clone. I. Definition according to profile of lymphokine activities and secreted proteins. J. Immunol. 136, 2348–2357.
Gately, M. K., Renzetti, L. M., Magram, J., Stern, A., Adorini, L., Gubler, U., and Presky, D. H. (1998) Interleukin-12/interleukin-12 receptor system: role in normal and pathologic immune responses. Annu. Rev. Immunol. 16, 495–521.
Paul, W. E. and Seder, R. A. (1994) Lymphocytes responses and cytokines. Cell 76, 241–251.
Scott, B., Liblau, R., Degermann, S., Marconi, L. A., Ogata, L., Caton, A. J., McDevitt, H. O., and Lo, D. (1994) Role for non-MHC genetic polymorphism in susceptibility to spontaneous autoimmunity. Immunity 1, 1–20.
Hsieh, C., Macatonia, S. E., O’Garra, A., and Murphy, K. M. (1995) T cell genetic background determines default T helper phenotype development in vitro. J. Exp. Med. 181, 713–731.
Reiner, S. L. and Locksley, R. M. (1995) Regulation of immunity to Leishmania major. Annu. Rev. Immunol. 13, 151–177.
Pfeiffer, C., Stein, J., Southwood, S., Ketelaar, H., Sette, A., and Bottomly, K. (1995) Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo. J. Exp. Med. 181, 1569–1574.
Nicholson, L. B., Greer, J. M., Sobel, R. A., Lees, M. B., and Kuchroo, V. K. (1995) Altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. Immunity 3, 397–405.
Hosken, N. A., Shibuya, K., Heath, A. W., Murphy, K. M., and O’Garra, A. (1995) Effect of antigen dose on CD4+helper cell phenotype development in a T cell receptor-αβ-transgenic model. J. Exp. Med. 182, 1579–1584.
Constant, S., Pfeiffer, C., Woodard, A., Pasqualini, T., and Bottomly, K. (1995) Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+T cells. J. Exp. Med. 182, 1591–1596.
Guéry, J.-C., Galbiati, F., Smiroldo, S., and Adorini, L. (1997) Non MHC-linked Th2 cell development induced by soluble protein administration predicts susceptibility to Leishmania major infection. J. Immunol. 159, 2147–2153.
Heinzel, F. P., Sadick, M. D., Holaday, B. J., Coffman, R. L., and Locksley, R. M. (1989) Reciprocal expression of interferon γ or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J. Exp. Med. 169, 59–72.
Guéry, J.-C., Galbiati, F., Smiroldo, S., and Adorini, L. (1996) Selective development of Th2 cells induced by continuous administration of low dose soluble proteins to normal and β2-micr°gl°bulin-deficient BALB/c mice. J. Exp. Med. 183, 485–497.
Howard, J. G., Hale, C., and Chan-Liew, W. L. (1980) Immunological regulation of experimental cutaneous leishmaniasis. I. Immunogenetic aspects of susceptibility to Leishmania tropica in mice. Parasite Immunol. 2, 303–310.
Degermann, S., Pria, E., and Adorini, L. (1996) Soluble protein but not peptide administration diverts the immune response of a clonal CD4+T cell population to the T helper 2 pathway. J. Immunol. 157, 3260–3269.
De Wit, D., Van Mechelen, M., Ryelandt, M., Figueiredo, A. C., Abramowicz, D., Goldman, M., et al. (1992) Injection of deaggregated gamma globulins in adult mice induces antigen-specific unresponsiveness of T helper type 1 but not type 2 lymphocytes. J. Exp. Med. 175, 9–14.
Burstein, H. J., Shea, C. M., and Abbas, A. K. (1992) Aqueous antigens induce in vivo tolerance selectively in IL-2-and IFN-γ-producing (Th1) cells. J. Immunol. 148, 3687–3691.
Romball, C. G. and Weigle, W. O. (1993) In vivo induction of tolerance in murine CD4+cell subsets. J. Exp. Med. 178, 1637–1644.
Forsthuber, T., Yip, H. C., and Lehmann, P. V. (1996) Induction of Th1 and Th2 immunity in neonatal mice. Science 271, 1728–1731.
Prat, M., Gribaudo, G., Comoglio, P. M., Cavallo, G., and Landolfo, S. (1984) Monoclonal antibodies against murine γ interferon. Proc. Natl. Acad. Sci. USA 81, 4515–4519.
Cherwinski, H., Shumacher, J., Brown, K., and Mosmann, T. (1987) Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally mono-specific bioassays, and monoclonal antibodies. J. Exp. Med. 166, 1229–1244.
Galbiati, F., Rogge, L., Guéry, J.-C., Smiroldo, S., and Adorini, L. (1998) Regulation of the interleukin (IL)-12 receptor β2 subunit by soluble antigen and IL-12 in vivo. Eur. J. Immunol. 28, 209–220.
Szabo, S. J., Jacobson, A. G., Gubler, U., and Murphy, K. M. (1995) Developmental commitment to the Th2 lineage by extinction of IL-12 signaling. Immunity 2, 665–675.
Perez, V. L., Lederer, J. A., Lichtman, A. H., and Abbas, A. K. (1995) Stability of Th1 and Th2 populations. Int. Immunol. 7, 869–875.
Manetti, R., Gerosa, F., Giudici, M. G., Biagiotti, R., Parronchi, P., Piccinni, M.-P., et al. (1994) Interleukin 12 induces stable priming for interferon-γ (IFN-γ) production during differentiation of human T helper (Th) cells and transient IFN-γ production in established Th2 cell clones. J. Exp. Med. 179, 1273–1283.
Sornasse, T., Larenas, P. V., Davis, K. A., De Vries, J. E., and Yssel, H. (1996) Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+T cells, analyzed at the single-cell level. J. Exp. Med. 184, 473–483.
Szabo, S. J., Dighe, A. S., Gubler, U., and Murphy, K. M. (1997) Regulation of the interleukin (IL)-12R β2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J. Exp. Med. 185, 817–824.
Rogge, L., Barberis-Maino, L., Biffi, M., Passini, N., Presky, D. H., Gubler, U., and Sinigaglia, F. (1997) Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J. Exp. Med. 185, 825–831.
Presky, D. H., Yang, H., Minetti, L. J., Chua, A. O., Nabavi, N., Wu, C.-Y., Gately, M. K., and Gubler, U. (1996) Functional interleukin-12 receptor complex is composed of two β type cytokine receptor subunits. Proc. Natl. Acad. Sci. USA 93, 14,002–14,007.
Constant, S., Sant’Angelo, D., Pasqualini, T., Taylor, T., Levin, D., Flavell, R., and Bottomly, K. (1995) Peptide and protein antigen require distinct antigen-presenting cell subsets for the priming of CD4+T cells. J. Immunol. 154, 4915–4923.
Guéry, J.-C., Ria, F., Galbiati, F., Smiroldo, S., and Adorini, L. (1997) Mode of protein antigen administration determines preferential presentation of pep-tide-class II complexes by lymph node dendritic or B cells. Int. Immunol. 9, 9–15.
Saoudi, A., Simmonds, S., Huitinga, I., and Mason, D. W. (1995) Prevention of experimental allergic encephalomyelitis in rats by targeting autoantigen to B cells: 244 evidence that the protective mechanism depends on changes in the cytokine response and migratory properties of autoantigen-specific T cells. J. Exp. Med. 182, 335–344.
Guéry, J. C., Ria, F., Galbiati, F., and Adorini, L. (1997) Normal B cells fail to secrete IL-12. Eur. J. Immunol. 27, 1632–1639.
Koch, F., Stanzl, U., Jennewein, P., Janke, K., Heufler, C., Kaempgen, E., Romani, N. and Schuler, G. (1996) High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J. Exp. Med. 184, 741–746.
Cella, M., Scheidegger, D., Palmer-Lehmann, K., Lane, P., Lanzavecchia, A., and Alber, G. (1996) Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J. Exp. Med. 184, 747–752.
Gorham, J. D., Guler, M. L., Steen, R. G., Mackey, A. J., Daly, M. J., Frederick, K., Detrich, W. F., and Murphy, K. M. (1996) Genetic mapping of a murine locus controlling development of T helper 1/T helper 2 type responses. Proc. Natl. Acad. Sci. USA 93, 12,467–12,471.
Mocci, S. and Coffman, R. L. (1995) Induction of a Th2 population from a polarized Leishmania-specific Th1 population by in vitro culture with IL-4. J. Immunol. 154, 3779–3787.
Murphy, E., Shibuya, K., Hosken, N., Openshaw, P., Maino, V., Davis, K., Murphy, K., and O’Garra, A. (1996) Reversibility of T helper 1 and 2 population is lost after long term stimulation. J. Exp. Med. 183, 901–913.
Mocci, S. and Coffman, R. L. (1997) Mechanism of in vitro T helper cell type 1 to T helper cell type 2 switching in highly polarized Leishmania major-specific T cell populations. J. Immunol. 158, 1559–1564.
Nabors, G. S., Afonso, L. C. C., Farrell, J. P., and Scott, P. (1995) Switch from a type 2 to a type 1 T helper cell response and cure of established Leishmania majorinfection in mice is induced by combined therapy with interleukin 12 and Pentostam. Proc. Natl. Acad. Sci. USA 92, 3142–3146.
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Galbiati, F., Adorini, L. (2000). Protocol for Diversion of a CD4+Response to theT-Helper 2 Cell Pathway. In: Solheim, J.C. (eds) Antigen Processing and Presentation Protocols. Methods in Molecular Biology, vol 156. Humana Press. https://doi.org/10.1385/1-59259-062-4:233
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DOI: https://doi.org/10.1385/1-59259-062-4:233
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Print ISBN: 978-0-89603-745-8
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