Viral phenotype affects the thymic production of new T cells in HIV-1-infected children

Abstract

To determine whether viral phenotype has any effect on thymic production of new T cells in HIV-1-infected children. Differences in CD4+ T-cell counts and a marker of thymic output [T-cell antigen receptor (TCR) rearrangement excision circles (TRECs)], between HIV-1-infected children with non-syncytium-inducing (NSI) and syncytium-inducing (SI) viral strains were determined. A cross-sectional study in 90 samples from vertically HIV-1-infected-children (median age 4.9 years) treated with combination therapy, and a longitudinal study in three children that underwent a change from NSI to SI phenotype were carried out. Viral load, viral phenotype, CD4+ T-cell counts, and quantification of TRECs values were determined. Children with SI virus showed significant lower levels of CD4+ T cells and a lower thymic production of new T cells than children with NSI. These reductions were independent of the treatment and the age of the children. However, there were no differences in viral load with the phenotype between those groups. In children with both NSI and SI viral phenotype, there was a significant correlation between CD4+ T-cell counts and TRECs values. The decrease of CD4+ T cells in presence of T-tropic viruses would be mainly due to a lower production of new CD4+ T cells as consequence of the inhibitory effect of these T-tropic strains on thymic function. This effect is not due either to the amount of circulating virus or to the replication kinetics of those strains, but rather depends on the ability of T-tropic viruses to infect T-cell precursors using CXCR4 receptors, which are highly expressed in immature thymocytes.