APOPTOTIC DEPLETION OF CD4-CELLS IN IDIOPATHIC CD4+ T-LYMPHOCYTOPENIA( T)

Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic i nfections characteristic of the acquired immune deficiency syndrome, h as been reported in the absence of any known etiology. The pathogenesi s of this syndrome, a subset of idiopathic CD4+ T lymphocytopenia (ICL ), is uncertain. We report that CD4+ T cells from seven of eight ICL p atients underwent accelerated programmed cell death, a process facilit ated by T cell receptor cross-linking. Apoptosis was associated with e nhanced expression of Fas and Fas ligand in unstimulated cell populati ons, and partially inhibited by soluble anti-Fas mAb. In addition, apo ptosis was suppressed by aurintricarboxylic acid, an inhibitor of calc ium-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 s table, 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 apopto sis 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 tha t patients with idiopathic loss of CD4+ T lymphocytes linked to clinic al immune suppression have evidence for accelerated T cell apoptosis i n vitro that may be pathophysiologic and amenable to therapy with apop tosis inhibitors.