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Published online 10 October 2005 doi:10.1084/jem.20051100
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 8, 1063-1073
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ARTICLE

Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing

Bengt Johansson-Lindbom1, Marcus Svensson1, Oliver Pabst2, Caroline Palmqvist1, Gabriel Marquez3, Reinhold Förster2, and William W. Agace1

1 Immunology Section, Lund University, BMC I-13, 221 84 Lund, Sweden
2 Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany
3 Departamento de Immunologia y Oncologia, Centro Nacional de Biotecnologia/Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Cantoblanco, 28040 Madrid, Spain

CORRESPONDENCE William W. Agace: William.Agace{at}immuno.lu.se

Gut-associated lymphoid tissue (GALT) dendritic cells (DCs) display a unique ability to generate CCR9+{alpha}4ß7+ gut-tropic CD8+ effector T cells. We demonstrate efficient induction of CCR9 and {alpha}4ß7 on CD8+ T cells in mesenteric lymph nodes (MLNs) after oral but not intraperitoneal (i.p.) antigen administration indicating differential targeting of DCs via the oral route. In vitro, lamina propria (LP)–derived DCs were more potent than MLN or Peyer's patch DCs in their ability to generate CCR9+{alpha}4ß7+ CD8+ T cells. The integrin {alpha} chain CD103 ({alpha}E) was expressed on almost all LP DCs, a subset of MLN DCs, but on few splenic DCs. CD103+ MLN DCs were reduced in number in CCR7/ mice and, although CD8+ T cells proliferated in the MLNs of CCR7/ mice after i.p. but not oral antigen administration, they failed to express CCR9 and had reduced levels of {alpha}4ß7. Strikingly, although CD103+ and CD103 MLN DCs were equally potent at inducing CD8+ T cell proliferation and IFN-{gamma} production, only CD103+ DCs were capable of generating gut-tropic CD8+ effector T cells in vitro. Collectively, these results demonstrate a unique function for LP-derived CD103+ MLN DCs in the generation of gut-tropic effector T cells.


Abbreviations used: 7-AAD, 7-amino-actinomycin D; CFSE, carboxyfluorescein diacetate succinimidyl ester; CT, cholera toxin; GALT, gut-associated lymphoid tissue; IEL, intraepithelial lymphocyte; LP, lamina propria; MLN, mesenteric LN; PLN, peripheral lymph node; PP, Peyer's patch.


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