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Discovery and initial characterization of Th9 cells: the early years

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Abstract

The launch of the Th1/Th2 concept represented a decisive breakthrough concerning our understanding of how very diverse immune reactions can be regulated by functionally different T helper subpopulations via the secretion of different panels of cytokines. In this context, IL-9 was identified to be produced by T helper cell lines in addition to Th2 cytokines IL-4 and IL-5. Detailed analyses revealed that IL-9 production of mouse CD4+ T helper cells was dependent on a combination of IL-2, IL-4, and TGF-β. Roughly a decade later, it was found that TGF-β can also induce the development of CD4+ Treg cells. This finding engendered a series of studies on the central role of TGF-β for cytokine-mediated T helper cell differentiation which elucidated that IL-4 curbed the Treg cell-promoting effect of TGF-β while TGF-β impaired the Th2-promoting capacity of IL-4. Instead, TGF-β in combination with IL-4 induced the development of CD4+ T helper cells that preferentially produced IL-9 and that were different from Th2 cells which originally were thought to be the main source of IL-9. In addition, adoptive transfer of such IL-9-producing CD4+ T helper cells was shown to cause the development of colitis and peripheral neuritis. Hence, the unique cytokine expression pattern in combination with the inflammatory in vivo phenotype led to the designation of Th9 cells as a new CD4+ T helper subpopulation.

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Notes

  1. ConA is a lectin (carbohydrate-binding protein) obtained from Canavalia ensiformis (Jack Bean) and represents a polyclonal T cell stimulator/T cell mitogen.

  2. PAGE: Polyacrylamide gel electrophoresis; common analytical technique to determine the molecular weight of an unknown protein.

  3. PPD: Glycerol extract of Mycobacterium tuberculosis [22].

  4. LNC.4: lymph node cells expanded in the presence of IL-4 that exhibited a Th2 phenotype.

  5. Accessory cells: irradiated spleen cells or bone marrow-derived macrophages.

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Acknowledgements

We thank Dr. Karen Lingnau and Dr. Matthias Klein for the critical reading of our manuscript.

Tobias Bopp and Edgar Schmitt are supported by the Deutsche Forschungsgemeinschaft (DFG), grants SCHM 1014/5-1 (T.B. and E.S.)

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Authors and Affiliations

  1. Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, Bd. 708, 55131, Mainz, Germany

    Edgar Schmitt & Tobias Bopp

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  1. Edgar Schmitt
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Correspondence to Edgar Schmitt.

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This article is a contribution to the special issue on Th9 Cells in Immunity and Immunopathological Diseases - Guest Editors Mark Kaplan and Markus Neurathâ

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Schmitt, E., Bopp, T. Discovery and initial characterization of Th9 cells: the early years. Semin Immunopathol 39, 5–10 (2017). https://doi.org/10.1007/s00281-016-0610-0

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