Long-term inhibition of murine lupus by brief simultaneous blockade of the B7/CD28 and CD40/gp39 costimulation pathways.
Long-term inhibition of murine lupus by brief simultaneous blockade of the B7/CD28 and CD40/gp39 costimulation pathways.
复制标题
通过短暂同时阻断 B7/CD28 和 CD40/gp39 共刺激途径来长期抑制小鼠狼疮。
DOI：
10.4049/jimmunol.159.7.3104
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发表时间：
1997
影响因子：
4.4
通讯作者：
D. Wofsy
中科院分区：
文献类型：
--
作者：
D. Daikh;B. Finck;P. S. Linsley;D. Hollenbaugh;D. Wofsy
NZB/NZW F1(B/W)小鼠的狼疮可以通过持续给予CTLA4Ig和生命早期用阻断CD40/gp39相互作用的单抗进行短暂治疗来延缓。我们试图确定CTLA4Ig的短期治疗是否可以为B/W小鼠提供持续的益处，以及是否可以通过阻断B7/CD28和CD40/gp39通路来产生协同效应。我们发现，在疾病开始时短程使用CTLA4Ig只会产生短期的益处。然而，当CTLA4Ig与抗gp39联合使用时，对自身抗体的产生和肾脏疾病有长期的抑制作用。两周疗程后10个月，这些小鼠中有70%存活，而仅接受抗gp39或CTLA4Ig治疗的小鼠分别只有18%和0%。这些发现表明，短暂同时阻断B7/CD28和CD40/gp39共刺激通路可以产生在停止治疗后持续很长时间的益处。
Murine lupus in NZB/NZW F1 (B/W) mice can be retarded by sustained administration of CTLA4Ig and by brief treatment early in life with mAb that block CD40/gp39 interactions. We sought to determine whether brief therapy with CTLA4Ig could provide sustained benefit in B/W mice and whether a synergistic effect could be derived by blockade of both the B7/CD28 and the CD40/gp39 pathways. We found that a short course of CTLA4Ig at the onset of disease produced only short-term benefit. However, when CTLA4Ig was combined with anti-gp39, there was long-lasting inhibition of autoantibody production and renal disease. Ten months after the 2-wk course of therapy, 70% of these mice were alive, compared with only 18% and 0% of those that received only anti-gp39 or CTLA4Ig, respectively. These findings demonstrate that brief simultaneous blockade of the B7/CD28 and CD40/gp39 costimulation pathways can produce benefit that lasts long after treatment has been discontinued.