期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 35, 页码 14584-14589出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1112188108
关键词
antibody therapy; Qa-1; T helper subsets
资金
- National Institutes of Health [AI 037562]
- Novo Nordisk
- National Research Service [T32 CA070083]
- Swedish Research Council
- National Natural Science Foundation of China
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 (T-H) subsets: follicular T-H cells and T(H)17 cells. Both CD4(+) T-H 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 T-H and T(H)17 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.
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