Jürgen Westermann, MD; Britta Engelhardt, MD; Jörg C. Hoffmann, MD
T cells play an important role in the pathogenesis of chronic and autoimmune inflammatory diseases. They are found in high numbers in involved tissues, such as the lamina propria of the gut in patients with Crohn disease. Modifying T-cell number and function may therefore be of therapeutic value.
In principle, two mechanisms may be responsible for the development of such T-cell infiltrates: 1) an increased rate of T-cell immigration into involved tissues or 2) an increased proliferation rate, decreased T-cell death (apoptosis) rate, and prolonged retention of T cells already in the tissue. Based on the theory that T cells selectively target affected tissues through organ-specific adhesion-molecule pathways, current anti-adhesion-molecule therapy aims to interfere selectively with T-cell entry to stop tissue damage.
However, the traffic of labeled T cells in unmanipulated animals shows that the entry of T-cell subsets into tissues is not organ-specific, even under conditions of differing adhesion molecule and chemokine receptor expression. In contrast, within various tissues, both movement and survival of T-cell subsets differ considerably. These observations suggest that the differential expression of adhesion molecules and chemokine receptors on T cells serves at least two functions in vivo. First, during migration of T cells out of the bloodstream, the different adhesion-molecule pathways provide redundancy, which guarantees that T-cell subsets are able to enter the different tissues in sufficient numbers (security). Second, adhesion molecules and chemokine receptors mediate T-cell interactions within the tissue that are characteristic for each subset and each microenvironment and determine the nature of the ensuing immune response (selectivity). Shifting the focus of anti-adhesion-molecule therapy toward the T cells in diseased tissue may lead to new treatment options.
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Westermann J, Engelhardt B, Hoffmann JC. Migration of T Cells in Vivo: Molecular Mechanisms and Clinical Implications. Ann Intern Med. 2001;135:279-295. doi: 10.7326/0003-4819-135-4-200108210-00013
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Published: Ann Intern Med. 2001;135(4):279-295.
Gastroenterology/Hepatology, Inflammatory Bowel Disease.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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