A NOVEL POPULATION OF CD4(-REACTIVE T-CELLS LYSES TARGET-CELLS EXPRESSING CD56()CD56(+) MYELIN)NEURAL CELL-ADHESION MOLECULE/

CD56 is a member of the neural cell adhesion molecule family expressed on cells of the central nervous system and also on NK cells. Previous studies suggest the involvement of CD56 in effector-to-target cell co njugation mediated by NK cells. It was shown recently that CD56 is als o expressed by subpopulations of CD8(+) and CD4(+) T cells. The presen t study describes the functional characteristics of CD4(+)CD56(+) T ce ll lines established from blood of multiple sclerosis patients by stim ulation with myelin basic protein (MBP). CD4(+)CD56(+), MBP-specific T cell lines were able to lyse MBP-pulsed target cells in an HLA class II-restricted fashion. At the same time, they mediated MHC-unrestricte d lysis of CD56(+) target cells such as CD56(+) lymphoid or glial tumo r cells, but not of the typical NK target, K562. A number of experimen tal results including separation of CD4(+)CD56(+) T cells into CD56 hi gh and low expressing populations, cold target inhibition, as well as killing of CD56-transfected cells indicate that homotypic CD56 interac tions are involved in the MHC-unrestricted lysis. CD56 interactions ar e not sufficient but are required for effector/target interaction. Our findings raise the possibility that CD4(+)CD56(+) T cells sharing pro perties of bath typical Ag-specific Th0-like T cells and NK cells migh t be involved in damage of tissues expressing CD56/neural cell adhesio n molecule, such as the central nervous system. Thus, we provide evide nce for a novel mechanism that could lead to organ-specific autoreacti vity.