Intestinal attraction: CCL25 functions in effector lymphocyte recruitment to the small intestine.

A large surface area and continuous exposure to the outside environment through food intake make the intestines an ideal location for the growth and/or entry of pathogenic microorganisms and parasites. It is therefore not surprising that large numbers of lymphocytes are associated with the intestines within specialized gut-associated lymphoid tissues (GALT) and in the intestines themselves (1). Within the intestines, lymphocytes are localized in two main compartments, the lamina propria (LP) and the intestinal epithelium (IE). Intestinal intraepithelial lymphocytes (IELs) consist mainly of cytotoxic T cells and have been divided into two subsets, type a and type b, based on their mode of antigen recognition (2). Responses of type a IELs are MHC restricted and directed against peptides derived from invading pathogens. Type b IELs display limited T cell receptor (TCR) diversity (both αβ and γδ TCRs are utilized), are not restricted by classical MHC molecules, and are thought to be largely autoreactive, recognizing nonpolymorphic stress-induced proteins displayed by infected or damaged epithelial cells. Lamina propria lymphocytes (LPLs) and type a IELs are believed to be derived from lymphocytes that recognized antigen in GALT, but the molecules that direct their migration to the intestines are not completely understood (3). In this issue of the JCI, Svensson et al. (4) demonstrate that expression of the chemokine receptor CCR9 is selectively maintained on CD8+ T cells activated in the GALT and that neutralization of the CCR9 ligand CCL25 strongly inhibits the accumulation of these cells in the type a IEL compartment (Figure 1). These results mark the first direct demonstration of a functional role for a chemokine/receptor pair in normal lymphocyte localization to an intestinal effector site.