Autoreactive T cells mediate NK cell degeneration in autoimmune disease.
Emerging evidence indicates that NK cells play an important and complex role in autoimmune disease. Humans with autoimmune diseases often have reduced NK cell numbers and compromised NK cell functions. Mechanisms underlying this NK cell degeneration and its biological significance are not known. In this study we show that, in an experimental model of human autoimmune myasthenia gravis induced by a self-Ag, the acetylcholine receptor, NK cells undergo proliferation during the initiation of autoimmunity, followed by significant degeneration associated with the establishment of the autoreactive T cell response. We show that NK cell degeneration was mediated by IL-21 derived from autoreactive CD4(+) T cells, and that acetylcholine receptor-immunized IL-21R-deficient mice, with competent NK cells, developed exacerbated autoimmunity. Thus, NK cell degeneration may serve as a means evolved by the immune system to control excessive autoimmunity.
Liu
Ruolan
R
Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 West Thomas Road, Phoenix, AZ 85013, USA.
Van Kaer
Luc
L
La Cava
Antonio
A
Price
Mary
M
Campagnolo
Denise I
DI
Collins
Mary
M
Young
Deborah A
DA
Vollmer
Timothy L
TL
Shi
Fu-Dong
FD
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015551:Autoimmunity / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation; D018920:Coculture Techniques; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D053655:Receptors, Interleukin-21; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D000098546:Interleukin-21
C508117:IL21R protein, human; C508118:Il21r protein, mouse; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D018123:Receptors, Interleukin; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21