The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20080039
The Journal of Experimental Medicine, Vol. 205, No. 11, 2483-2490
The Rockefeller University Press, 0022-1007 $30.00
© Hammerschmidt et al.
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BRIEF DEFINITIVE REPORT

 Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo

Swantje I. Hammerschmidt1, Manuela Ahrendt2, Ulrike Bode2, Benjamin Wahl1, Elisabeth Kremmer3, Reinhold Förster1, and Oliver Pabst1

1 Institute of Immunology and 2 Institute of Anatomy, Hannover Medical School, 30625 Hannover, Germany
3 Institute of Molecular Immunology, National Research Center for Environment and Health, 81377 Munich, Germany

CORRESPONDENCE Oliver Pabst: Pabst.Oliver{at}MH-Hannover.de

T cells primed in the gut-draining mesenteric lymph nodes (mLN) are imprinted to express {alpha}4β7-integrin and chemokine receptor CCR9, thereby enabling lymphocytes to migrate to the small intestine. In vitro activation by intestinal dendritic cells (DC) or addition of retinoic acid (RA) is sufficient to instruct expression of these gut-homing molecules. We report that in vivo stroma cells, but not DC, allow the mLN to induce the generation of gut tropism. Peripheral LN (pLN) transplanted into the gut mesenteries fail to support the generation of gut-homing T cells, even though gut-derived DC enter the transplants and prime T cells. DC that fail to induce {alpha}4β7-integrin and CCR9 in vitro readily induce these factors in vivo upon injection into mLN afferent lymphatics. Moreover, uniquely mesenteric but not pLN stroma cells express high levels of RA-producing enzymes and support induction of CCR9 on activated T cells in vitro. These results demonstrate a hitherto unrecognized contribution of stromal cell delivered signals, including RA, on the imprinting of tissue tropism in vivo.

© 2008 Hammerschmidt et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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