Human LFA-1 governs T cell immune surveillance of the skin
The human integrin LFA-1 (alphaLbeta2) is broadly expressed on leukocytes and involved in various intercellular adhesions. We report complete LFA-1 deficiency due to inherited alphaL (CD11a) deficiency in otherwise healthy adults of various ancestries with skin lesions due to commensal papillomaviruses. The patients have no history of invasive infections characteristic of children with inherited deficiency of beta2 (CD18), which forms heterodimers with alphaL, alphaM, alphaX, or alphaD. The absence of LFA-1 does not compromise the development or function of any leukocyte subset. However, the transendothelial migration of skin-tropic CLA+ T cells is severely impaired, resulting in their selective sequestration in the blood. Conversely, alternative integrins mediate the extravasation of other leukocytes, including other T-cell subsets, to other tissues. Human LFA-1 is required for steady-state T-cell homing to the skin and control of papillomaviruses but is otherwise largely redundant. Integrin-mediated T-cell compartmentalization is thus essential for organ-selective immune surveillance.