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Development of Th1-type immune responses requires the type I cytokine receptor TCCR

Nature volume 407, pages 916–920 (2000)Cite this article

Abstract

On antigen challenge, T-helper cells differentiate into two functionally distinct subsets, Th1 and Th2, characterized by the different effector cytokines that they secrete1. Th1 cells produce interleukin (IL)-2, interferon-γ (IFN-γ) and lymphotoxin-β, which mediate pro-inflammatory functions critical for the development of cell-mediated immune responses, whereas Th2 cells secrete cytokines such as IL-4, IL-5 and IL-10 that enhance humoral immunity1,2. This process of T-helper cell differentiation is tightly regulated by cytokines. Here we report a new member of the type I cytokine receptor family, designated T-cell cytokine receptor (TCCR). When challenged in vivo with protein antigen, TCCR-deficient mice had impaired Th1 response as measured by IFN-γ production. TCCR-deficient mice also had increased susceptibility to infection with an intracellular pathogen, Listeria monocytogenes. In addition, levels of antigen-specific immunoglobulin-γ2a, which are dependent on Th1 cells, were markedly reduced in these mice. Our results demonstrate the existence of a new cytokine receptor involved in regulating the adaptive immune response and critical to the generation of a Th1 response.

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Figure 1: Amino-acid sequence and tissue distribution of TCCR.
Figure 2: Targeting of the TCCR gene by homologous recombination.
Figure 3: Antigen-induced cytokine production and proliferation by lymph-node cells from TCCR-deficient mice.
Figure 4: Effect on IgG subclass concentrations and sensitivity to L. monocytogenes infection.
Figure 5: In vitro induction of T-helper cell differentiation and proliferation.

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Acknowledgements

We thank the Genentech micro-injection lab, DNA sequencing lab and M. Vasser and the DNA synthesis lab for their support; J. Tepper, S. Fong, M. Aguet and R Schreiber for their advice on this project; and J. Ligos for help with graphics.

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Author notes

  1. Iqbal S. Grewal and Frederic J. de Sauvage: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Molecular Oncology,

    Qi Chen, Nico Ghilardi, Hua Wang, Thad Baker, Iqbal S. Grewal & Frederic J. de Sauvage

  2. Immunology,

    Hua Wang, Thad Baker & Iqbal S. Grewal

  3. Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, 94080, California, USA

    Ming-Hong Xie & Austin Gurney

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  1. Qi Chen
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Correspondence to Frederic J. de Sauvage.

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Chen, Q., Ghilardi, N., Wang, H. et al. Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature 407, 916–920 (2000). https://doi.org/10.1038/35038103

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