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Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells

Abstract

Whereas naive T cells migrate only to secondary lymphoid organs1,2, activation by antigen confers to T cells the ability to home to non-lymphoid sites3,4. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered5,6,7. Thus, oral antigens induce effector/memory cells that express essential receptors for intestinal homing, namely the integrin α4β7 and CCR9, the receptor for the gut-associated chemokine TECK/CCL25 (refs 6, 8, 9). Here we show that this imprinting of gut tropism is mediated by dendritic cells from Peyer's patches. Stimulation of CD8-expressing T cells by dendritic cells from Peyer's patches, peripheral lymph nodes and spleen induced equivalent activation markers and effector activity in T cells, but only Peyer's patch dendritic cells induced high levels of α4β7, responsiveness to TECK and the ability to home to the small intestine. These findings establish that Peyer's patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomical sites most likely to contain their cognate antigen.

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Figure 1: Antigen stimulation of CD8+ cells by DCs from PP, spleen and PLN induces equivalent activation markers and effector activity, but only PP DCs induce high expression of α4β7 integrin.
Figure 2: CD8PP-DC are significantly more responsive than CD8PLN-DC or CD8Sp-DC to the gut-associated chemokine TECK/CCL25.
Figure 3: CD8PP-DC home to the small intestine.

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Acknowledgements

We are grateful to H. Ploegh for providing reagents and mice. We thank I. Dodge, B. Harnisch, G. Cheng, N. Barteneva, C. Halin, E. Schott and S. Feske for advice and technical assistance. J.R.M. is indebted to Ingrid Ramos for constant support. This work was supported by grants from NIH to U.H.v.A.; from Fondecyt to J.R.M., M.R.B. and M.R.; and from MIFAB (financed in part by Ministerio de Planificación y Cooperación, Chile) to M.R. W.W. is a fellow of the Max Kade Foundation. J.R.M. was supported in part by fellowships from Fundación Andes and the Pew Foundation.

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Correspondence to Ulrich H. von Andrian.

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Mora, J., Bono, M., Manjunath, N. et al. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature 424, 88–93 (2003). https://doi.org/10.1038/nature01726

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