Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity

The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propr ia lymphocytes migrate to thymus-expressed chemokine (TECK). This attractio n is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor e xpressed at high levels by essentially all CD4(+) and CD8(+) T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9(+), and lymphocytes from other tissues including tonsils, lung, infla med liver, normal or inflamed skin, inflamed synovium and synovial fluid, b reast milk, and seminal fluid are universally CCR9(-). TECK expression is a lso restricted to the small intestine: immunohistochemistry reveals that in tense anti-TECK reactivity characterizes crypt epithelium in the jejunum an d ileum, but not in other epithelia of the digestive tract (including stoma ch and colon), skin, lung, or salivary gland. These results imply a restric ted role for lymphocyte CCR9 and its ligand TECK in the small intestine, an d provide the first evidence for distinctive mechanisms of lymphocyte recru itment that may permit functional specialization of immune responses in dif ferent segments of the gastrointestinal tract. Selective expression of chem okines by differentiated epithelium may represent an important mechanism fo r targeting and specialization of immune responses.