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

J. Rodrigo Mora; Maria Rosa Bono; N. Manjunath; Wolfgang Weninger; Lois L. Cavanagh; Mario Rosemblatt; Ulrich H. Von Andrian

doi:10.1038/nature01726

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

J. Rodrigo Mora, Maria Rosa Bono, N. Manjunath, Wolfgang Weninger, Lois L. Cavanagh, Mario Rosemblatt, Ulrich H. Von Andrian^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

942 Scopus citations

Abstract

Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to non-lymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. 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.

Original language	English
Pages (from-to)	88-93
Number of pages	6
Journal	Nature
Volume	424
Issue number	6944
DOIs	https://doi.org/10.1038/nature01726
State	Published - 2003
Externally published	Yes

Bibliographical note

Funding Information:
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.

Funding Information:
Acknowledgements We thank A. Ray for advice on scanning electron microscopy, D. Weigel for providing the pDW137 vector, members of Yanofsky laboratory for comments, and H. Chang and P. Golshani for technical assistance. A.P. received a scholarship from the Ananda Mahidol Foundation, and this work was supported by a grant from the National Science Foundation (to M.Y.).

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Cite this

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title = "Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells",

abstract = "Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to non-lymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. 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.",

author = "Mora, {J. Rodrigo} and Bono, {Maria Rosa} and N. Manjunath and Wolfgang Weninger and Cavanagh, {Lois L.} and Mario Rosemblatt and {Von Andrian}, {Ulrich H.}",

note = "Funding Information: 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 Planificaci{\'o}n y Cooperaci{\'o}n, Chile) to M.R. W.W. is a fellow of the Max Kade Foundation. J.R.M. was supported in part by fellowships from Fundaci{\'o}n Andes and the Pew Foundation. Funding Information: Acknowledgements We thank A. Ray for advice on scanning electron microscopy, D. Weigel for providing the pDW137 vector, members of Yanofsky laboratory for comments, and H. Chang and P. Golshani for technical assistance. A.P. received a scholarship from the Ananda Mahidol Foundation, and this work was supported by a grant from the National Science Foundation (to M.Y.).",

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doi = "10.1038/nature01726",

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AU - Bono, Maria Rosa

AU - Manjunath, N.

AU - Weninger, Wolfgang

AU - Cavanagh, Lois L.

AU - Rosemblatt, Mario

AU - Von Andrian, Ulrich H.

N1 - Funding Information: 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. Funding Information: Acknowledgements We thank A. Ray for advice on scanning electron microscopy, D. Weigel for providing the pDW137 vector, members of Yanofsky laboratory for comments, and H. Chang and P. Golshani for technical assistance. A.P. received a scholarship from the Ananda Mahidol Foundation, and this work was supported by a grant from the National Science Foundation (to M.Y.).

PY - 2003/7/3

Y1 - 2003/7/3

N2 - Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to non-lymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. 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.

AB - Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to non-lymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. 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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JO - Nature

JF - Nature

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ER -

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

Abstract

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