Expression of cutaneous lymphocyte-associated antigen by CD8+ T cells specific for a skin-tropic virus

Abstract

Introduction Models of homing of memory T cells to sites of antigen challenge incorporate an initial step of rolling adher-ence to activated vascular endothelium (1). The cuta-neous lymphocyte-associated antigen (CLA) is a fucose-containing carbohydrate that can decorate P-selectin glycoprotein ligand-1 on T cells (2). CLA is expressed on the surface of most T cells recovered from skin, and on about 5–10% of circulating CD8 + T cells (3). E-selectin (also known as ELAM and CD62E) is expressed by venular endothelial cells in inflamed skin, oral mucosa, and the female genital tract (4–6). An epi-tope related, although not identical (7), to CLA can interact with E-selectin, leading to the tethering and rolling of CLA-expressing cells in vitro (2). This inter-action has been hypothesized to direct lymphocyte traf-ficking to skin in vivo. However, the role of CLA-asso-ciated E-selectin ligands in the trafficking of virus-specific CD8 + T cells to cutaneous sites of infec-tion has not previously been investigated. Herpes simplex virus type 2 (HSV-2) causes intermit-tent lytic infection of skin and genital mucosa, with or without lesion formation and symptoms. Replicating virus is mostly limited to the epidermis or mucosal squamous keratinocytes (8, 9). During symptomatic recurrent infection, antigen-specific CD4 + T cells and NK cells infiltrate the subjacent dermis by day 2 of lesion formation, while CD8 + T cell infiltration, local virus-specific cytotoxic activity, and viral clearance typ-ically occur a few days later (10). HSV-specific CD8 +