Adhesive interactions in contact dermatitis

Pathological inflammation, such as occurs in allergic contact dermatitis and delayed-type hypersensitivity, requires migration into the inflamed region of lymphocytes and granulocytes, as well as dendritic cells (DCs) and other antigen-presenting cells (APCs). Adhesive interactions of these migratory cells with the vascular endothelium and with other cell types and extracellular macromolecules must therefore be tightly regulated . The integrin b2 subunit, also called CD18, is found in several heterodimeric forms that are expressed by myeloid cells and is central to many of these interactions. The importance of CD18 in host defense is evident because patients with leukocyte adhesion deficiency type I (LAD I), who carry mutations in the corresponding human gene, are prone to bacterial infection. Grabbe et al. now report that in a mouse knockout model lacking CD18 entirely, animals are unable to mount the usual inflammatory responses to allergens. At the cellular level, the defect is specific for the extravasation of T cells, since APCs migrate normally into areas exposed to allergen. These findings generally confirm cell culture and intravital microscopic studies indicating that b1 integrins can substitute for b2 in monocytes and DCs but not in lymphocytes. Interestingly, CD18-deficient T cells appear to be spontaneously hyperactivated, suggesting that adhesion through CD18 helps suppress autoimmune activation.

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