핵심기술
특허 / 논문
| Amelioration of Mercury-Induced Autoimmunity by 4-1BB. |
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| 등록일 :2022-11-03 09:20 조회수 :2,446 |
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Amelioration of Mercury-Induced Autoimmunity by 4-1BB.
Vinay DS, Kim JD, Kwon BS
Abstract In certain strains of mice, subtoxic doses of HgCl2 (mercuric chloride; mercury) induce a complex autoimmune condition characterized by the production of antinucleolar IgG Abs, lymphoproliferation, increased serum levels of IgG1/IgE Abs, and deposition of renal immune complexes. 4-1BB is an important T cell costimulatory molecule that has been implicated in T cell proliferation and cytokine production, especially production of IFN-γ. To elucidate T cell control mediated by the 4-1BB signaling pathway in this syndrome, we assessed the effect of administering agonistic anti-4-1BB mAb on mercury-induced autoimmunity. Groups of A.SW mice (H-2s) received mercury/control Ig or mercury/anti-4-1BB or PBS alone. Anti-4-1BB mAb treatment resulted in a dramatic reduction of mercury-induced antinucleolar Ab titers, serum IgG1/IgE induction, and renal Ig deposition. These effects may be related to the present finding that anti-4-1BB mAb decreases B cell numbers and function. The anti-4-1BB mAb-treated mercury group also showed a marked reduction in Th2-type cytokines but an increase in Th1-type cytokines and chemokines. Increased IFN-γ production due to anti-4-1BB mAb treatment appears to be responsible for the observed B cell defects because neutralization of IFN-γ in vivo substantially restored B cell numbers and partly restored IgG1/IgE. Collectively, our results indicate that 4-1BB mAb can down-regulate mercury-induced autoimmunity by affecting B cell function in an IFN-γ-dependent manner and thus, preventing the development of autoantibody production and tissue Ig deposition.
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