Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia

被引:82
作者
Laurence, J
Mitra, D
Steiner, M
Lynch, DH
Siegal, FP
StaianoCoico, L
机构
[1] CORNELL UNIV, COLL MED, DEPT SURG, NEW YORK, NY 10021 USA
[2] IMMUNEX RES & DEV CORP, SEATTLE, WA 98101 USA
[3] LONG ISL JEWISH MED CTR, DIV HEMATOL, NEW HYDE PK, NY 11042 USA
关键词
aurintricarboxylic acid; cell death; programmed; immunologic deficiency syndromes; T lymphocyte;
D O I
10.1172/JCI118464
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, has been reported in the absence of any known etiology. The pathogenesis of this syndrome, a subset of idiopathic CD4+ T lymphocytopenia (ICL), is uncertain. We report that CD4+ T cells from seven of eight ICL patients underwent accelerated programmed cell death, a process facilitated by T cell receptor cross-linking. Apoptosis was associated with enhanced expression of Fas and Fas ligand in unstimulated cell populations, and partially inhibited by soluble anti-Fas mAb. In addition, apoptosis was suppressed by aurintricarboxylic acid, an inhibitor of calcium-dependent endonucleases and proteases, in cells from four of seven patients. The in vivo significance of these findings was supported by three factors: the absence of accelerated apoptosis in persons with stable, physiologic CD4 lymphopenia without clinical immune deficiency; detection of serum antihistone H2B autoantibodies, one consequence of DNA fragmentation, in some patients; and its selectivity, with apoptosis limited to the CD4 population in some, and occurring among CD8+ T cells predominantly in those individuals with marked depletion of both CD4+ and CD8+ peripheral T lymphocyte subsets. These data suggest that patients with idiopathic loss of CD4+ T lymphocytes linked to clinical immune suppression have evidence for accelerated T cell apoptosis in vitro that may be pathophysiologic and amenable to therapy with apoptosis inhibitors.
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页码:672 / 680
页数:9
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