Defective apoptosis in lymphocytes and the role of IL-2 in autoimmune hematologic cytopenias

被引:29
作者
Shenoy, S [1 ]
Mohanakumar, T
Chatila, T
Tersak, J
Duffy, B
Wang, R
Thilenius, ARB
Russell, JH
机构
[1] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[4] Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA
[5] Childrens Hosp Pittsburgh, Div Pediat Hematol Oncol, Pittsburgh, PA 15213 USA
关键词
Fas signaling; apoptosis; activation-induced cell death; IL-2; autoimmune cytopenia;
D O I
10.1006/clim.2001.5017
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Fas-mediated signaling is important for lymphocyte elimination. We investigated lymphocytes for Pas-signaling defects in 20 pediatric patients with chronic hematologic autoimmunity. In 5 of 20 (25%), there was profound resistance to exogenous Fast-mediated lysis, Fas mAb, and anti-CD3, FasL function, though variable, was not significantly different from that of simultaneously evaluated controls. Only 1 patient had a Fas mutation and manifestations of autoimmune lymphoproliferative syndrome. In contrast, lymphocytes from his clinically normal mother with the same mutation were normally sensitive to FasL. In 3 patients, normal Fas-mediated lysis was restored with rhIL-2. IL-2 had no effect in the other 2 patients. Activation and proliferation functions of IL-2 were normal in all 5, We conclude that altered Fas signaling, independent of Fas mutations, can precipitate hematologic autoimmunity. IL-2 can rescue some lymphocytes from this defect. In IL-2 refractory cases, a persistently defective response to IL-2 continues to confer a lymphocyte survival advantage. Hence, altered Fas pathway signaling with or without defective IL-2 responses should be considered in the etiology of hematologic autoimmunity, (C) 2001 Academic Press.
引用
收藏
页码:266 / 275
页数:10
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