Viral load and CD69 molecule expression on freshly isolated and cultured mitogen-stimulated lymphocytes of children with perinatal HIV-1 infection

Abstract

HIV-1 in adults changes the proportion of mitogen-stimulated lymphocytes expressing the CD69 activation molecule, but little is known about this molecule expression on lymphocytes of HIV-1-infected (HIV-1+) children. Freshly isolated CD3+, CD4+, CD8+ and CD19+ and phytohaemagglutinin (PHA)-stimulated CD3+, CD4+ and CD8+ lymphocytes co-expressing CD69 were investigated cross-sectionally (adopting a MoAb double-staining technique) in 24 HIV-1+ children with severe disease and given anti-retroviral therapy and in 24 age-matched healthy children. CD69 results in HIV-1+ children were correlated with plasma HIV-1 RNA load prospectively determined. HIV-1+ compared with healthy children had higher frequencies of freshly isolated CD3+CD69+ (2.4 ± 2.2% versus 0.9 ± 0.5%; P = 0.002) and CD8+CD69+ (1.5 ± 1.1% versus 0.5 ± 0.2%; P < 0.0001) lymphocytes. The frequencies of CD4+CD69+ and CD19+CD69+ lymphocytes were similar. High vital load correlated with an elevated proportion of freshly isolated CD3+CD69+ and CD8+CD69+ lymphocytes. HIV-1+ children showed reduced frequencies of PHA- stimulated CD3+CD69+ (60.7 ± 7.6% versus 86.1 ± 7.6%; P < 0.001), CD4+CD69+ (73.6 ± 18.2% versus 92.6 ± 5.1%; P < 0.001), and CD8+CD69+ (51.0 ± 19.1% versus 65.3 ± 15.4%; P = 0.007) lymphocytes. Virologic worsening within 6 months correlated with a low proportion of PHA-stimulated CD3+CD69+ and CD8+CD69+ lymphocytes. CD69 molecule expression reflected the coexistence of immune activation and immune deficiency in HIV-1 infection. Changes partly differed from those observed in HIV-1+ adults. CD8+CD69+ (but not CD4+CD69+) lymphocyte proportion correlated with virologic course, and an impaired ability of CD8+ lymphocytes to express CD69 upon PHA stimulation preceded a virologic worsening.