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 and Ulrich H. von Andrian ()
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J. Rodrigo Mora: Harvard Medical School
Maria Rosa Bono: Universidad de Chile, Fundación Ciencia para la Vida, and Millennium Institute for Fundamental and Applied Biology (MIFAB)
N. Manjunath: Harvard Medical School
Wolfgang Weninger: Harvard Medical School
Lois L. Cavanagh: Harvard Medical School
Mario Rosemblatt: Universidad de Chile, Fundación Ciencia para la Vida, and Millennium Institute for Fundamental and Applied Biology (MIFAB)
Ulrich H. von Andrian: Harvard Medical School

Nature, 2003, vol. 424, issue 6944, 88-93

Abstract: 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.

Date: 2003
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DOI: 10.1038/nature01726

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