Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.
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.
Laurence
J
J
Laboratory of AIDS Virus Research, Cornell University Medical College, New York, New York 10021, USA.
Mitra
D
D
Steiner
M
M
Lynch
D H
DH
Siegal
F P
FP
Staiano-Coico
L
L
D000328:Adult; D017209:Apoptosis; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000209:etiology*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000187:drug effects; D018344:T-Lymphocytopenia, Idiopathic CD4-Positive / Q000150:complications / Q000209:etiology*; D013629:Tamoxifen / Q000494:pharmacology; D019014:fas Receptor
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D013629:Tamoxifen; D001312:Aurintricarboxylic Acid