APOPTOSIS OF CD4(-CELLS ISOLATED IMMEDIATELY EX-VIVO CORRELATES WITH DISEASE SEVERITY IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION() AND CD8(+) T)

Apoptosis of CD4(+) and CD8(+) T cells has been shown in peripheral bl ood mononuclear cells (PBMCs) from HIV-infected adults analyzed after overnight culture. Because cell death may be an artifact of in vitro c ulture, and because there is little information on apoptosis in pediat ric HIV disease, we undertook a cross-sectional analysis of apoptosis in PBMCs analyzed im mediately ex vivo in HIV-infected children and ad ults. PBMCs from 22 children, four adolescents, and nine adults and se ronegative age-matched control subjects were stained for CD4 and CD8 s urface markers, Apoptotic cells were detected in a newly characterized how cytometric assay by diminished forward and increased side scatter , Children with the most advanced disease had 9.9% (SEM 1.8) apoptotic CD4(+) T cells above control, significantly higher than in asymptomat ic patients [0.4% (SEM 2.3)], those with mild disease [2.2% (SEM 1.83) ], and those with moderate disease [2.5 (SEM 3.6)] (p = 0.015). The pe rcentages of both CD4(+) and CD8(+) T cell apoptosis were directly rel ated to CD4(+) T cell depletion (R-2 = 0.23: p = 0.006: n = 32 and R-2 = 0.2; p = 0.012; n = 30, respectively), Patients who responded to an tiretroviral therapy with the greatest increase in CD4(+) T cell perce ntage had the least CD4(+) T cell apoptosis (R-2 = 0.15; p = 0.1; n = 19). These findings show that the rate or extent of T cell death by ap optosis percentage. of T fell apoptosis is significantly increased in HIV-infected children, The observed correlation of both CD4(+) and CD8 (+) T cell apoptosis with CD4(+) T cell depletion suggests that apopto sis plays a role in HIV pathogenesis and may be a useful marker of dis ease activity.