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A novel population of CD4+CD56+ myelin-reactive T cells lyses target cells expressing CD56/neural cell adhesion molecule

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Author: Vergelli, M. · Le, H. · Noort, J.M. van · Dhib-Jalbut, S. · McFarland, H. · Martin, R.
Type:article
Date:1996
Institution: TNO Preventie en Gezondheid
Source:Journal of Immunology, 2, 157, 679-688
Identifier: 233400
Keywords: Biology · Cd8 antigen · HLA antigen class 2 · Major histocompatibility antigen · Nyelin basic protein · Nerve cell adhesion molecule · Animal cell · Antigen expression · Cell adhesion · Controlled study · Major histocompatibility complex · Mouse · Multiple sclerosis · Natural killer cell · Protein family · T lymphocyte subpopulation · Target cell · Antigens, CD4 · Antigens, CD56 · Biological Markers · Cytotoxicity, Immunologic · Epitopes · Histocompatibility Antigens Class II · Humans · Immunophenotyping · Killer Cells, Natural · Myelin Basic Proteins · Neural Cell Adhesion Molecules · T-Lymphocyte Subsets · Tumor Cells, Cultured

Abstract

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