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

Laurence, J. ; Mitra, D. ; Steiner, M. ; Lynch, D. H. ; Siegal, F. P. ; Staiano-Coico, L. (1996) Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia Journal of Clinical Investigation, 97 (3). pp. 672-680. ISSN 0021-9738

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Related URL: http://dx.doi.org/10.1172/JCI118464

Abstract

Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, ahs 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+ 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.

Item Type:Article
Source:Copyright of this article belongs to American Society of Clinical Investigation.
ID Code:103038
Deposited On:05 Feb 2017 16:48
Last Modified:05 Feb 2017 16:48

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