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CD70+ antigen-presenting cells control the proliferation and differentiation of T cells in the intestinal mucosa

Nature Immunology volume 6, pages 698–706 (2005)Cite this article

Abstract

One unresolved issue in gut immunity is how mucosal T lymphocytes are activated and which antigen-presenting cell (APC) is critical for the regulation of this process. We have identified a unique population of APCs that is exclusively localized in the lamina propria. These APCs constitutively expressed the costimulatory molecule CD70 and had antigen-presenting functions. After oral infection of mice with Listeria monocytogenes, proliferation and differentiation of antigen-specific T cells occurred in the gut mucosa in situ and blockade of CD70 costimulation abrogated the mucosal T cell proliferation and effector functions. Thus, a potent CD70-dependent stimulation via specialized tissue-specific APCs is required for the proliferation and differentiation of gut mucosal T cells after oral infection.

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Figure 1: Presence of a unique CD70+ cell population in the gut lamina propria.
Figure 2: Nonhematopoietic origin of CD70+ cells.
Figure 3: Antigen presenting function of CD70+ APCs.
Figure 4: Proliferation and differentiation of T cells occurs in the intestinal mucosa after oral L. monocytogenes infection.
Figure 5: Lta−/− mice do not generate a gut mucosal T cell response.
Figure 6: Treatment with anti-CD70 abrogates T cell proliferation in the lamina propria and intraepithelial lymphocyte compartment.

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Acknowledgements

We thank A. Schlesinger for help with ELISPOT assays. Supported by the US National Institutes of Health (AI46566 to N.M.).

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Authors and Affiliations

  1. The CBR Institute for Biomedical Research and Department of Pediatrics, Boston, 02115, Massachusetts, USA

    Amale Laouar, Viraga Haridas, Dorothy Vargas & N Manjunath

  2. Dana-Farber Cancer Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Xia Zhinan

  3. Department of Microbiology, University of Birmingham, Alabama, 35294, USA

    David Chaplin

  4. Laboratory for Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands

    Rene A W van Lier

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  1. Amale Laouar
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Correspondence to N Manjunath.

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Supplementary information

Supplementary Fig. 1

Phenotype and morphology of CD70+ APC and their presence in MuMT and RAG-1−/− mice. (PDF 226 kb)

Supplementary Fig. 2

Purity of cell preparations and capture of Lm by CD70+ APC. (PDF 369 kb)

Supplementary Fig. 3

CD70 blockade selectively inhibits mucosal T cell expansion. (PDF 156 kb)

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Laouar, A., Haridas, V., Vargas, D. et al. CD70+ antigen-presenting cells control the proliferation and differentiation of T cells in the intestinal mucosa. Nat Immunol 6, 698–706 (2005). https://doi.org/10.1038/ni1212

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