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

Clinical Immunology : the Official Journal of the Clinical Immunology Society
S ShenoyJ H Russell

Abstract

Fas-mediated signaling is important for lymphocyte elimination. We investigated lymphocytes for Fas-signaling defects in 20 pediatric patients with chronic hematologic autoimmunity. In 5 of 20 (25%), there was profound resistance to exogenous FasL-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.

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Citations

Nov 6, 2007·La Revue de médecine interne·M Michel
Feb 17, 2006·European Journal of Haematology·Feng ZhangMing Hou
Apr 22, 2005·Critical Reviews in Oncology/hematology·Bin ZhouZhong Chao Han
Jul 26, 2005·Seminars in Hematology·John W Semple, John Freedman
Dec 12, 2003·Journal of Pediatric Hematology/oncology·John W Semple
Nov 23, 2013·Frontiers of Medicine·Xinguang LiuJun Peng
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gudrun StraussKlaus-Michael Debatin
May 16, 2018·Frontiers in Immunology·Maurice SwinkelsA J Gerard Jansen

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