Basic and clinical immunology: Markers of cell death-activation in lymphocytes of vertically HIV-infected children naive to highly active antiretroviral therapy: The role of age

Background: Apoptosis plays a major role in depleting CD4 ⁺ lymphocytes during infection with HIV-1. Few data exist on its role during HIV infection of children. Sensitivity of peripheral blood lymphocytes (PBLs) to apoptotic stimuli and the importance of the patient's age remain unclear. Objectives: We sought to analyze the following: (1) markers of cell death-activation (CD95, CD45 isoforms, and CD28) in PBLs from vertically HIV-infected children of different ages before highly active antiretroviral therapy; (2) changes in other PBL populations; (3) PBL sensitivity to cell death and mitochondrial damages; and (4) role of age during progression of infection. Methods: Cell culture techniques and flow cytometry were used to analyze surface antigens, PBL susceptibility to apoptosis, or PBL susceptibility to change of mitochondrial membrane potential. Results: Donor age had a strong negative correlation with numbers of CD4 ⁺ and CD8 ⁺ T cells. Virgin T lymphocyte (CD45RA ⁺, CD95 ^-) levels and those of CD95 ⁺ cells showed no correlation with the children's clinical status but did show a correlation with patient age. CD28 ^- T lymphocytes were markedly augmented in HIV-infected children but were unrelated to stage of infection or age. A relevant decrease in B lymphocytes and an increase in natural killer cells were also found. Finally, PBLs from HIV-positive children had a marked tendency to undergo apoptosis and mitochondrial damage. Conclusion: Changes in PBL phenotype, increased expression of CD95, and high sensitivity to apoptosis suggest that a precocious aging of the immune system occurs in HIV-infected children.