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

Jeffrey Laurence, Debashis Mitra, Melissa Steiner, David H. Lynch, Frederick P. Siegal, Lisa Staiano-Coico

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)672-680
Number of pages9
JournalJournal of Clinical Investigation
Volume97
Issue number3
DOIs
StatePublished - 1 Feb 1996
Externally publishedYes

Keywords

  • T lymphocyte
  • aurintricarboxylic acid
  • cell death, programmed
  • immunologic deficiency syndromes

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