A novel population of CD4+CD56+ myelin-reactive T cells lyses target cells expressing CD56/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 conjugation mediated by NK cells. It was shown recently that CD56 is also expressed by subpopulations of CD8+ and CD4+ T cells. The present study describes the functional characteristics of CD4+CD56+ T cell lines established from blood of multiple sclerosis patients by stimulation 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-unrestricted lysis of CD56+ target cells such as CD56+ lymphoid or glial tumor cells, but not of the typical NK target, K562. A number of experimental results including separation of CD4+CD56+ T cells into CD56 high and low expressing populations, cold target inhibition, as well as killing of CD56-transfected cells indicate that homotypic CD56 interactions are involved in the MHC-unrestricted lysis. CD56 interactions are not sufficient but are required for effector/target interaction. Our findings raise the possibility that CD4+CD56+ T cells sharing properties of both typical Ag-specific Th0-like T cells and NK cells might be involved in damage of tissues expressing CD56/neural cell adhesion molecule, such as the central nervous system. Thus, we provide evidence for a novel mechanism that could lead to organ-specific autoreactivity.
Vergelli
M
M
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Le
H
H
van Noort
J M
JM
Dhib-Jalbut
S
S
McFarland
H
H
Martin
R
R
D015415:Biomarkers; D015704:CD4 Antigens / Q000032:analysis*; D019002:CD56 Antigen / Q000032:analysis* / Q000096:biosynthesis / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D015704:CD4 Antigens; D019002:CD56 Antigen; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D019006:Neural Cell Adhesion Molecules