Skip to main content

Protocol for Diversion of a CD4+Response to theT-Helper 2 Cell Pathway

  • Protocol
Antigen Processing and Presentation Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 156))

  • 734 Accesses

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 ).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. 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.

    CAS  PubMed  Google Scholar 

  2. 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.

    Article  CAS  PubMed  Google Scholar 

  3. Paul, W. E. and Seder, R. A. (1994) Lymphocytes responses and cytokines. Cell 76, 241–251.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  Google Scholar 

  5. 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.

    Article  CAS  PubMed  Google Scholar 

  6. Reiner, S. L. and Locksley, R. M. (1995) Regulation of immunity to Leishmania major. Annu. Rev. Immunol. 13, 151–177.

    Article  CAS  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    CAS  PubMed  Google Scholar 

  16. 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.

    Article  PubMed  Google Scholar 

  17. 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.

    CAS  PubMed  Google Scholar 

  18. Romball, C. G. and Weigle, W. O. (1993) In vivo induction of tolerance in murine CD4+cell subsets. J. Exp. Med. 178, 1637–1644.

    Article  CAS  PubMed  Google Scholar 

  19. Forsthuber, T., Yip, H. C., and Lehmann, P. V. (1996) Induction of Th1 and Th2 immunity in neonatal mice. Science 271, 1728–1731.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  CAS  PubMed  Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. 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.

    Article  CAS  PubMed  Google Scholar 

  25. 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.

    Article  CAS  PubMed  Google Scholar 

  26. 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.

    Article  CAS  PubMed  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  CAS  PubMed  Google Scholar 

  30. 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.

    CAS  PubMed  Google Scholar 

  31. 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.

    Article  PubMed  Google Scholar 

  32. 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.

    Article  CAS  PubMed  Google Scholar 

  33. 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.

    Article  PubMed  Google Scholar 

  34. 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.

    Article  CAS  PubMed  Google Scholar 

  35. 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.

    Article  CAS  PubMed  Google Scholar 

  36. 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.

    Article  CAS  PubMed  Google Scholar 

  37. 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.

    CAS  PubMed  Google Scholar 

  38. 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.

    Article  CAS  PubMed  Google Scholar 

  39. 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.

    CAS  PubMed  Google Scholar 

  40. 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.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Humana Press Inc.

About this protocol

Cite this protocol

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

Download citation

  • DOI: https://doi.org/10.1385/1-59259-062-4:233

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-745-8

  • Online ISBN: 978-1-59259-062-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics