2B4, A NEW MEMBER OF THE IMMUNOGLOBULIN GENE SUPERFAMILY, IS EXPRESSED ON MURINE DENDRITIC EPIDERMAL T-CELLS AND PLAYS A FUNCTIONAL-ROLE INTHEIR KILLING OF SKIN TUMORS

Dendritic epidermal T cells (DETC), which are skin-specific members of the tissue-resident gamma delta T-cell family, are characterized by t heir potential to kill selected tumor targets by a non-major histocomp atibility complex (MHC)-restricted mechanism. We have recently identif ied a new receptor molecule, 2B4, that appears to be associated with n on-MHC-restricted recognition of tumor targets by natural killer cells . The purpose of this study was to determine whether DETC express 2B4 molecules, and, if so, to assess their functional roles in DETC-mediat ed killing of tumor targets. Short-term DETC lines as well as DETC fre shly procured from skin expressed surface 2B4, as detected with a spec ific monoclonal antibody. Removal of interleukin (IL)-2 from DETC cult ures caused substantial reduction in 2B4 expression levels as well as a reduction in cytotoxic capacity against YAC-1 targets in a standard Cr-51-release assay. Conversely, exposure to IL-2, but not to IL-7, el evated both 2B4 expression and cytotoxicity. To assess the functional roles played by surface 2B4, we pretreated DETC lines with anti-2B4 an tibody and then tested for their killing potential. Anti-2B4, but not the control antibody, augmented their capacity to lyse YAC-1 targets ( Cr-51-release assays) and to disrupt the monolayers of Pam-212-transfo rmed keratinocytes (visual assessment). Thus, we conclude that DETC ex press, in an IL-2-dependent manner, 2B4 molecules, which may play a un ique role in the killing of skin-derived tumors.