IVIg attenuates T cell-mediated killing of human neurons.
Beneficial effects of intravenous immunoglobulin (IVIg) in relapsing-remitting multiple sclerosis (MS) have been described, including a decrease of brain atrophy. We have previously shown that activated T cells kill neurons in culture. In this manuscript, we show that the pretreatment of activated T cells with IVIg attenuates T cell neurotoxicity. This is attributed to the ability of IVIg to decrease the adhesion of T cells onto neurons, possibly through an effect on LFA-1, and by lowering the levels of Fas and FasL on T cells. Our results are relevant to understanding how therapies affect the MS disease process.
Janke
Angela D
AD
Department of Oncology, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive, Calgary, Alberta, Canada T2N 4N1.
Giuliani
Fabrizio
F
Yong
V Wee
VW
D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D053222:Fas Ligand Protein; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology*; D009474:Neurons / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016756:Immunoglobulins, Intravenous; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors; D019014:fas Receptor