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A critical role for interleukin 4 in activating alloreactive CD4 T cells

Nature Immunology volume 1, pages 257–261 (2000)Cite this article

Abstract

To generate antigen-specific responses, T cells and antigen presenting cells (APCs) must physically associate with each other and elaborate soluble factors that drive the full differentiation of each cell type. Immediately after T cell activation, CD4 T cells can produce both interferon γ (IFN-γ) and interleukin 4 (IL-4) before polarization into distinct T helper subsets. Inhibition of IL-4 during mixed allogeneic lymphocyte culture resulted in a defect in the ability of APCs to generate sufficient costimulatory signals for activation of alloreactive T cells. In vivo, a deficiency in IL-4 production inhibited the activation of alloreactive IL-2–, IL-4– and IFN-γ–producing CD4 T cells in mice challenged with allogeneic skin grafts, resulting in prolonged skin graft survival. Thus, production of IL-4 by CD4 T cells helps activate alloreactive T cells by affecting APC function.

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Figure 1: (a) Neutralization of IL-4 in mixed allogeneic cultures inhibits activation of cytokine-producing CD4 T cells.
Figure 2: (a) Neutralization of IL-4 in mixed allogeneic culture does not lead to T cell anergy.
Figure 3: Neutralization of IL-4 in vitro prevents up-regulation of B7.1 and B7.2 surface expression on APC.
Figure 4: Neutralization or absence of IL-4 in vivo results in prolonged skin allograft survival.
Figure 5: (a) Neutralization of IL-4 in vivo prevents expansion of CD4 T cells.
Figure 6: (a) Neutralization of IL-4 in vivo inhibits the activation of alloreactive CD4 T cells.

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Acknowledgements

We thank S. Pillai, J. J. Lafaille and H. Winn for critical review of the manuscript; N. Cretin for assistance with skin grafts; P. Heeger for advice on performing ELISPOT assays; and D. H. Sachs for monoclonal antibodies 11B11, 2.43 and GK1.5. Supported in part by the National Institutes of Health grant RO1 AI43619 (to J.I.).

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  1. Tokihiko Sawada

    Present address: Kidney Center, Tokyo Women's Medical College, 8-1 Kawada-Cho Shinjuku, Tokyo, 162, Japan

Authors and Affiliations

  1. Transplantation Biology Research Center, Massachusetts General Hospital, MGH-East, Building 149, 13th Street, Boston, 02129, MA, USA

    Jessamyn Bagley, Tokihiko Sawada, Yin Wu & John Iacomini

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  1. Jessamyn Bagley
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  2. Tokihiko Sawada
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Correspondence to John Iacomini.

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Bagley, J., Sawada, T., Wu, Y. et al. A critical role for interleukin 4 in activating alloreactive CD4 T cells. Nat Immunol 1, 257–261 (2000). https://doi.org/10.1038/79811

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