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Mobilization of natural killer cells inhibits development of collagen-induced arthritis

Leavenworth, Jianmei W., Wang, Xiaoyang, Wenander, Carola Schellack, Spee, Pieter, Cantor, Harvey
Proceedings of the National Academy of Sciences of the United States of America 2011 v.108 no.35 pp. 14584-14589
collagen, disease course, humans, immune response, models, natural killer cells, rheumatoid arthritis
Although natural killer (NK) cells have been implicated in regulating immune responses, their ability to modulate disease development in autoimmune arthritis has not been analyzed. Here we investigate the contribution of NK cells to regulating collagen-induced arthritis, a well-characterized preclinical model of human rheumatoid arthritis. We find that the disease is induced by the combined action of two CD4+ T helper (TH) subsets: follicular TH cells and TH17 cells. Both CD4+ TH subsets are highly susceptible to lysis by NK cells after activation. Administration of antibody that activates NK cells through blockade of its inhibitory CD94/NKG2A receptor allows enhanced elimination of pathogenic follicular TH and TH17 cells and arrest of disease progression. These results suggest that antibody-dependent enhancement of NK activity may yield effective, previously undescribed therapeutic approaches to this autoimmune disorder.