Stromal Mesenteric Lymph Node Cells Are Essential for the Generation of Gut-homing T Cells in Vivo

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2008 Oct 15

PMID 18852290

Citations 158

Authors

Swantje I Hammerschmidt

Manuela Ahrendt

Ulrike Bode

Benjamin Wahl

Elisabeth Kremmer

Reinhold Forster

Oliver Pabst

Affiliations

Soon will be listed here.

Abstract

T cells primed in the gut-draining mesenteric lymph nodes (mLN) are imprinted to express alpha4beta7-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 alpha4beta7-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.

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