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

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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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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