The chemokine TECK is expressed by thymic and intestinal epithelial cells and attracts double- and single-positive thymocytes expressing the TECK receptor CCR9

Abstract

Chemokines are key regulators of migration in lymphoid tissues. In the thymus, maturing thymocytes move from the outer capsule to the inner medulla and thereby interact with different types of stromal cells that control their maturation and selection. In the process of searching for molecules specifically expressed at different stages of mouse thymic differentiation, we have characterized the cDNA coding for the thymus-expressed chemokine (TECK) and its receptor CCR9. The TECK receptor gene was isolated and shown to be localized on the mouse chromosome 9F1-F4. Thymic dendritic cells have been initially thought to be a prevalent source of TECK. In contrast, our results indicate that thymic epithelial cells constitute the predominant source of TECK. Consistent with the latter distribution, the TECK receptor is highly expressed by double-positive thymocytes, and TECK can chemoattract both double-positive and single-positive thymocytes. The TECK transcript is also abundantly expressed in the epithelial cells lining the small intestine. In conclusion, the interplay of TECK and its receptor CCR9 is likely to have a significant role in the recruitment of developing thymocytes to discrete compartments of the thymus.

Impaired Accumulation of Antigen-Specific CD8 Lymphocytes in Chemokine CCL25-Deficient Intestinal Epithelium and Lamina Propria

“…I nteractions between the chemokine CCL25 and its receptor CCR9 are involved in thymic development and in the generation of gut-specific immunological memory (1)(2)(3). In the thymus, CCL25-CCR9 interactions appear to play an important role in the migration of early T cells into the cortex from the subcapsular zone after successful TCR␤ gene rearrangement (4 -7).…”

“…In the gut, CCL25 is strongly expressed by epithelial cells lining the small intestinal villi (2,13), but is less prominently expressed in the colon (2,14,15). The vast majority of small-intestinal T and B lymphocytes express high levels of CCR9 (3,13).…”

“…Exons 1-6 are shown as gray boxes. The restriction sites are B (BglII), E (EcoR V), H (HindIII), and X (XbaI) (2). Targeting vector used for the deletion of the 3Ј end of exon 2 (starting at the BglII restriction site and including ATG), exon 3 and exon 4 (containing the four cysteine residues crucial for the folding of CCL25).…”

A Role for CCR9 in T Lymphocyte Development and Migration

“…Expression of CCL25/thymus-expressed chemokine was initially detected in medullary dendritic cells (9), but recent experiments indicate that it is also expressed by thymic epithelial cells in both cortex and medulla (10,11). Interestingly, CCL25 is also expressed in fetal thymus, raising the possibility that it may participate in recruiting T progenitor cells to the thymus (12).…”

“…Interestingly, CCL25 is also expressed in fetal thymus, raising the possibility that it may participate in recruiting T progenitor cells to the thymus (12). The only other known site of CCL25 production is the epithelial layer of the small intestine (11,(13)(14)(15). Thus, CCL25 may also be important for the development, homeostasis, and/or function of mucosal T lymphocytes.…”