However, we observed a statistically significant decrease in total IgG, IgG1 and IgG3 levels (< 005) in all HIV-infected children after 1 year on HAART

However, we observed a statistically significant decrease in total IgG, IgG1 and IgG3 levels (< 005) in all HIV-infected children after 1 year on HAART. absolute counts of naive CD4+ and CD8+ T cell subsets were increased significantly (< 005). CD4+ CD45RAhi+ CD62L+, CD4+ CD45RA+ and CD4+ CD38+ percentages, and the CD8+ CD45RAhi+ CD62L+ counts reached similar values to the control group. Also, CD8+ CD45RO+ CD38+ and CD8+ CD45RO+ percentages, and CD8+ CD45RO+ CD38+ absolute counts (< 005) decreased with respect to the baseline. Lymphoproliferative responses to pokeweed mitogen (PWM) before HAART were lower in HIV-infected children than the control group, but they recovered to normal levels after a year on HAART. Tumour necrosis factor (TNF)-and interferon (IFN)-production by PHA-activated peripheral blood mononuclear cells (PBMC) was lower before HAART (< 0001), but reached similar levels to the control group 1 year after HAART. In HIV-infected children IgG, IgG1 and IgG3 plasma levels decreased significantly after HAART. The immune system reconstitution induced by HAART in HIV-infected children seems to be the consequence of decreased immune system activation and naive T cell reconstitution, mainly of thymic origin. Keywords: cytokine, HAART, HIV-infected children, immunoglobulin, T cell subsets, TREC INTRODUCTION HIV infection leads to a severe depletion of CD4+ T cells, phenotypic alterations of T cell subsets and a decline in thymic function which, in turn, produces a progressive impairment of functional immunity [1C3]. These alterations can be partially corrected after inhibition of HIV replication by highly active antiretroviral therapy (HAART) in HIV-infected children [4]. Thus, in HIV-infected children after severe depletion of T cells, HAART resulted in a consistent increase in CD4+ T cell counts [5C7] and T cell receptor excision circle (TREC) levels in young HIV-infected patients [8C10], even in advanced stages of HIV disease [11], or in children with virological failure (virological non-responders) [8,12]. These findings indicate Isochlorogenic acid A that recovery of thymic function is a pivotal event in immune reconstitution [12]. In children, the recovery of naive CD4+ T cells occurs more rapidly if treatment is started at a younger age, but after 1 year of viral replication control, patients of all ages have achieved the same level of restoration. Markers of chronic activation in CD8+ T cells persist after 1 year on HAART [13]. Moreover, HIV infection induces qualitative T cell abnormalities as a result of a decrease in lymphoproliferative response (LPR) to mitogens such as phytohaemagglutinin (PHA), pokeweed mitogen (PWM) or anti-CD3 plus anti-CD28 [2,14], as well as a desregulated production of cytokines [15], all of them more pronounced in advanced HIV disease. Thus, tumour necrosis factor-alpha (TNF-and interferon (IFN)-(Bender Medical Systems Diagnostics, Vienna, Austria). Concentrations were assayed in duplicate. Statistical analysis In all analyses, viral load (VL) and Rabbit Polyclonal to MMP12 (Cleaved-Glu106) TREC values were transformed to log10-scale in order to normalize their distribution. Cytokine production from PBMC stimulated with mitogens were corrected subtracting the cytokines values of unstimulated PBMC. PBMC proliferation is expressed as stimulation indexes (s.i.): Differences in characteristics among groups of children were analysed using the non-parametric test (MannCWhitney < 005). However, they did not reach values of TREC similar to those of the control groups. Table 3 TREC values, and percentages and absolute counts of naive CD4+ and CD8+ T cells in HIV-infected children on HAART = 0558; = 005), and percentages (= 0625; = 003) at the end of the study were found. However, we did not find a correlation among changes in TREC values and CD3+, CD8+ T cells or VL at the end of the study. CD4+ and CD8+ T cell subpopulations HIV-infected children at the study entry had percentages and absolute counts of naive (CD45RAhi+ CD62L+) CD4+ and CD8+ T cells lower than the control group, except for CD4+ CD38+ percentages and CD8+ CD45RA+ counts (Table 3). After 1 year on HAART, the percentages and absolute counts of naive CD4+ and CD8+ T cells subsets were increased significantly (< 005). More interestingly, CD4+ CD45RA+, CD4+ CD45RAhi+ CD62L+ and CD4+ CD38+ percentages, and CD8+ CD45RAhi+ CD62L+ counts reached after HAART similar values than the control group (Table 3). At the study entry, activated memory T cells (CD4+ CD45RO+ HLA-DR+ and CD8+ CD45RO+ CD38+) were higher Isochlorogenic acid A than the control group, but after 1 year on HAART we observed a significant decrease in the values of theses T cell subsets (< 005) with similar values to the control group. Memory CD4+ T cells (CD4+ CD45RO+) increased and memory CD8+ T cells (CD8+ CD45RO+) decreased at the end of study on HAART (< 005) (Table 4). We also analysed effector CD8+ T cells (CD8+ CD57+, CD8+ CD28- CD57+) and we found that HIV-infected children had higher values of CD8+ CD57+ and CD8+ CD28- Isochlorogenic acid A CD57+ than control group. However, these subsets did not decrease during follow-up (Table 4). Table.