A novel population of CD4+CD56+ myelin-reactive T cells lyses target cells expressing CD56/neural cell adhesion molecule
article
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. Chemicals/CAS: Antigens, CD4; Antigens, CD56; Biological Markers; Epitopes; Histocompatibility Antigens Class II; Myelin Basic Proteins; Neural Cell Adhesion Molecules
Topics
Cd8 antigenHLA antigen class 2Major histocompatibility antigenNyelin basic proteinNerve cell adhesion moleculeAnimal cellAntigen expressionCell adhesionControlled studyMajor histocompatibility complexMouseMultiple sclerosisNatural killer cellProtein familyT lymphocyte subpopulationTarget cellAntigens, CD4Antigens, CD56Biological MarkersCytotoxicity, ImmunologicEpitopesHistocompatibility Antigens Class IIHumansImmunophenotypingKiller Cells, NaturalMyelin Basic ProteinsNeural Cell Adhesion MoleculesT-Lymphocyte SubsetsTumor Cells, Cultured
TNO Identifier
233400
ISSN
00221767
Source
Journal of Immunology, 157(2), pp. 679-688.
Pages
679-688
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