Selective generation of gut tropic T cells in gut-associated lymphoid tissue (GALT): requirement for GALT dendritic cells and adjuvant

J Exp Med. 2003 Sep 15;198(6):963-9. doi: 10.1084/jem.20031244. Epub 2003 Sep 8.

Abstract

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 alpha4beta7 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+alpha4beta7+CD62Llow, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / metabolism*
  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Movement
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Integrin alpha4 / metabolism
  • Integrin beta Chains / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • L-Selectin / metabolism
  • Lymphocyte Activation
  • Lymphoid Tissue / cytology*
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CCR
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Adjuvants, Immunologic
  • CC chemokine receptor 9
  • Integrin beta Chains
  • Receptors, CCR
  • Receptors, Chemokine
  • integrin beta7
  • L-Selectin
  • Integrin alpha4