TY - JOUR
T1 - A novel population of CD4+CD56+ myelin-reactive T cells lyses target cells expressing CD56/neural cell adhesion molecule
AU - Vergelli, Marco
AU - Le, Hoang
AU - Van Noort, Johannes M.
AU - Dhib-Jalbut, Suhayl
AU - McFarland, Henry
AU - Martin, Roland
PY - 1996/7/15
Y1 - 1996/7/15
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8752917
AN - SCOPUS:0030002224
SN - 0022-1767
VL - 157
SP - 679
EP - 688
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -