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

Autor: Viganò, Alessandra, Pinti, Marcello, Nasi, Milena, Moretti, Laura, Balli, Fiorella, Mussini, Cristina, Bricalli, Dorella, Sala, Natascia, Bugarini, Roberto, Vella, Stefano, Principi, Nicola, Cossarizza, Andrea
Zdroj: The Journal of Allergy and Clinical Immunology; September 2001, Vol. 108 Issue: 3 p439-445, 7p
Abstrakt: 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. (J Allergy Clin Immunol 2001;108:439-45.)
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