Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Essay
  • Published:

Origins of the TH1-TH2 model: a personal perspective

Robert L. Coffman recounts how his work on immunoglobulin E regulation along with data from Tim Mosmann on the functional heterogeneity of T cell clones led to the T helper type 1–T helper type 2 hypothesis.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The principal stimulatory and inhibitory interactions between TH1 and TH2 cells, both directly and through their effector functions.

References

  1. Mosmann, T.R. & Coffman, R.L. Two types of mouse helper T-cell clone. Immunol. Today 8, 223–227 (1987).

    Article  CAS  Google Scholar 

  2. Mosmann, T.R. & Coffman, R.L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 7, 145–173 (1989).

    Article  CAS  Google Scholar 

  3. Liew, F.Y. TH1 and TH2 cells: a historical perspective. Nat. Rev. Immunol. 2, 55–60 (2002).

    Article  CAS  Google Scholar 

  4. Coffman, R.L. & Carty, J.A. T cell activity that enhances polyclonal IgE production and its inhibition by interferon-γ. J. Immunol. 136, 949–954 (1986).

    CAS  PubMed  Google Scholar 

  5. Mosmann, T.R., Cherwinski, H., Bond, M.W., Giedlin, M.A. & Coffman, R.L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348–2357 (1986).

    CAS  Google Scholar 

  6. Liew, F.Y. & Parish, C.R. Lack of a correlation between cell-mediated immunity to the carrier and the carrier-hapten helper effect. J. Exp. Med. 139, 779–784 (1974).

    Article  CAS  Google Scholar 

  7. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55–63 (1983).

    Article  CAS  Google Scholar 

  8. Vitetta, E.S. et al. T-cell-derived lymphokines that induce IgM and IgG secretion in activated murine B cells. Immunol. Rev. 78, 137–157 (1984).

    Article  CAS  Google Scholar 

  9. Bergstedt-Lindqvist, S., Sideras, P., MacDonald, H.R. & Severinson, E. Regulation of Ig class secretion by soluble products of certain T-cell lines. Immunol. Rev. 78, 25–50 (1984).

    Article  CAS  Google Scholar 

  10. Coffman, R.L. et al. B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells. J. Immunol. 136, 4538–4541 (1986).

    CAS  PubMed  Google Scholar 

  11. Mosmann, T.R., Bond, M.W., Coffman, R.L., Ohara, J. & Paul, W.E. T-cell and mast cell lines respond to B-cell stimulatory factor 1. Proc. Natl. Acad. Sci. USA 83, 5654–5658 (1986).

    Article  CAS  Google Scholar 

  12. Cher, D.J. & Mosmann, T.R. Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. J. Immunol. 138, 3688–3694 (1987).

    CAS  PubMed  Google Scholar 

  13. Yokota, T. et al. Isolation and characterization of lymphokine cDNA clones encoding mouse and human IgA-enhancing factor and eosinophil colony-stimulating factor activities: relationship to interleukin 5. Proc. Natl. Acad. Sci. USA 84, 7388–7392 (1987).

    Article  CAS  Google Scholar 

  14. Fiorentino, D.F., Bond, M.W. & Mosmann, T.R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J. Exp. Med. 170, 2081–2095 (1989).

    Article  CAS  Google Scholar 

  15. Mosmann, T.R. & Sad, S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol. Today 17, 138–146 (1996).

    Article  CAS  Google Scholar 

  16. Janeway, C.A., Jr. & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 20, 197–216 (2002).

    Article  CAS  Google Scholar 

  17. Powrie, F., Carlino, J., Leach, M.W., Mauze, S. & Coffman, R.L. A critical role for transforming growth factor-β but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RBlow CD4+ T cells. J. Exp. Med. 183, 2669–2674 (1996).

    Article  CAS  Google Scholar 

  18. Powrie, F., Correa-Oliveira, R., Mauze, S. & Coffman, R.L. Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity. J. Exp. Med. 179, 589–600 (1994).

    Article  CAS  Google Scholar 

  19. McKenzie, B.S., Kastelein, R.A. & Cua, D.J. Understanding the IL-23-IL-17 immune pathway. Trends Immunol. 27, 17–23 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I thank T. Mosmann for his role in the work recollected here; colleagues at DNAX and at other institutions for contributions to the development of the TH1-TH2 hypothesis; and S. Coffman, F. Barrat, E. Hessel and H. Kanzler for comments on the manuscript.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Coffman, R. Origins of the TH1-TH2 model: a personal perspective. Nat Immunol 7, 539–541 (2006). https://doi.org/10.1038/ni0606-539

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni0606-539

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing