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Brief Definitive Report

Bengt Johansson-Lindbom¹, Marcus Svensson¹, Marc-André Wurbel², Bernard Malissen², Gabriel Márquez³ and William Agace¹

¹ Immunology Section, Department of Cell and Molecular Biology, Lund University, BMC I-13, S-22184 Lund, Sweden
² Centre d'Imunnologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale–Centre National de la Recherche Scientifique–Université de la Méditerranée, Case 906, 13288 Marseille Cedex 9, France
³ Departamento de Inmunologia y Oncologia, Centro Nacional de Biotecnologia/Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Cantoblanco, 28040-Madrid, Spain

Address correspondence to Bengt Johansson-Lindbom, Immunology Section, Dept. of Cell and Molecular Biology, Lund University, BMC I-13, S-22184 Lund, Sweden. Phone: 46-46-2220313; Fax: 46-46-2224218; email: Bengt.Johansson_Lindbom{at}immuno.lu.se

In the current study, we address the underlying mechanism for the selective generation of gut-homing T cells in the gut-associated lymphoid tissues (GALT). We demonstrate that DCs in the GALT are unique in their capacity to establish T cell gut tropism but in vivo only confer this property to T cells in the presence of DC maturational stimuli, including toll-like receptor-dependent and -independent adjuvants. Thus, DCs from mesenteric LNs (MLNs), but not from spleen, supported expression of the chemokine receptor CCR9 and integrin ₄ß₇ by activated CD8⁺ T cells. While DCs were also required for an efficient down-regulation of CD62L, this function was not restricted to MLN DCs. In an adoptive CD8⁺ T cell transfer model, antigen-specific T cells entering the small intestinal epithelium were homogeneously CCR9⁺₄ß₇⁺CD62L^low, and this phenotype was only generated in GALT and in the presence of adjuvant. Consistent with the CCR9⁺ phenotype of the gut-homing T cells, CCR9 was found to play a critical role in the localization of T cells to the small intestinal epithelium. Together, these results demonstrate that GALT DCs and T cell expression of CCR9 play critical and integrated roles during T cell homing to the gut.

Key Words: lymphocytes • antigen-presenting cell • inflammation • chemokines • intestinal mucosa

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