Human LFA-1 governs T cell immune surveillance of the skin

Abstract

The human integrin lymphocyte function-associated antigen 1 (LFA-1; alpha L beta 2) is broadly expressed on leukocytes and involved in various intercellular adhesions. We report complete LFA-1 deficiency because of inherited alpha L (CD11a) deficiency in otherwise healthy adults of various ancestries with skin lesions due to commensal papillomaviruses. The patients had no history of invasive infections characteristic of children with inherited deficiency of beta 2 (CD18), which forms heterodimers with alpha L, alpha M (CD11b), alpha X (CD11c), or alpha D (CD11d). The development and function of leukocyte subsets are largely preserved in the absence of LFA-1. However, the transendothelial migration of skin-tropic cutaneous lymphocyte antigen (CLA)+ memory 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.