Regulation of experimental autoimmune encephalomyelitis by natural killer (NK) cells.
In this report, we establish a regulatory role of natural killer (NK) cells in experimental autoimmune encephalomyelitis (EAE), a prototype T helper cell type 1 (Th1)-mediated disease. Active sensitization of C57BL/6 (B6) mice with the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide induces a mild form of monophasic EAE. When mice were deprived of NK cells by antibody treatment before immunization, they developed a more serious form of EAE associated with relapse. Aggravation of EAE by NK cell deletion was also seen in beta 2-microglobulin-/- (beta 2m-/-) mice, indicating that NK cells can play a regulatory role in a manner independent of CD8+ T cells or NK1.1+ T cells (NK-T cells). The disease enhancement was associated with augmentation of T cell proliferation and production of Th1 cytokines in response to MOG35-55. EAE passively induced by the MOG35-55-specific T cell line was also enhanced by NK cell deletion in B6, beta 2m-/-, and recombination activation gene 2 (RAG-2)-/- mice, indicating that the regulation by NK cells can be independent of T, B, or NK-T cells. We further showed that NK cells inhibit T cell proliferation triggered by antigen or cytokine stimulation. Taken together, we conclude that NK cells are an important regulator for EAE in both induction and effector phases.
Zhang
B
B
Department of Demyelinating Disease and Aging, National Institute of Neuroscience, Tokyo, Japan.
Yamamura
T
T
Kondo
T
T
Fujiwara
M
M
Tabira
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000941:Antigens / Q000276:immunology; D000950:Antigens, Ly; D000954:Antigens, Surface; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D000911:Antibodies, Monoclonal; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D016207:Cytokines; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D001613:beta 2-Microglobulin; D007371:Interferon-gamma