Essential role of NK cells in IgG therapy for experimental autoimmune encephalomyelitis

• Published in: PloS one Vol. 8; no. 4; p. e60862
• Main Authors: Chong, Wai Po, Ling, Man To, Liu, Yinping, Caspi, Rachel R, Wong, Wai Man, Wu, Wutian, Tu, Wenwei, Lau, Yu Lung
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.04.2013; Public Library of Science (PLoS)
• Subjects: Adoptive Transfer; Amino Acid Sequence; Animal experimentation; Animals; Autoimmune diseases; Autoimmunity; Biology; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Proliferation - drug effects; Cytokines; Demyelinating Diseases - complications; Demyelinating Diseases - therapy; Dendritic cells; Development and progression; Drug dosages; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - complications; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - therapy; Experimental allergic encephalomyelitis; Forkhead Transcription Factors - metabolism; Foxp3 protein; Immunoglobulin G; Immunoglobulin G - therapeutic use; Immunoglobulins; Immunology; Immunoregulation; Interferon; Interferon-gamma - biosynthesis; Interleukin 17; Interleukin 2; Interleukin-17 - biosynthesis; Interleukin-2 - biosynthesis; Interleukin-2 - metabolism; Interleukin-2 Receptor alpha Subunit - metabolism; Interleukins; Intravenous administration; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Laboratories; Lymph nodes; Lymphocytes; Lymphocytes T; Medicine; Mice; Molecular Sequence Data; Multiple sclerosis; Natural killer cells; Receptors; Regulation; Rodents; T cell receptors; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Therapy; Transforming Growth Factor beta1 - pharmacology; United States > US; Maryland; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0060862

Intravenous immunoglobulin has long been used in treating autoimmune diseases, although mechanisms remain uncertain. Activating Fcγ receptors are receptors of IgG and reported to be essential in intravenous immunoglobulin (IVIG) therapy. Therefore, we hypothesized natural killer (NK) cells, which express abundant activating Fcγ receptors, are the potential cellular target. In experimental autoimmune encephalomyelitis (EAE), we demonstrated that IgG suppressed disease development in intact, but not in NK cell depleted mice. Adoptive transfer of IgG-treated NK cell could protect mice against EAE, and suppressed interferon γ and interleukin 17 production. The percentage of CD4(+)Foxp3(+) regulatory T cells was significantly increased. The increase of regulatory T cells was also observed in IgG-treated EAE mice but not in NK cell depleted mice. In vitro experiments confirmed that IgG-treated NK cells enhanced regulatory T cell induction from naïve CD4(+) T cells. Interestingly, cells from draining lymph nodes produced more interleukin 2 after the adoptive transfer of IgG-treated NK cells. We neutralized interleukin 2 and the induction of CD4(+)Foxp3(+) T cells by IgG-treated NK cells was significantly reduced. To our knowledge, we identified for the first time the critical role of NK cells in the mechanism of IgG-induced induction of Treg cells in treatment of autoimmunity.