Functional patterns of HIV-1-specific CD4 T-cell responses in children are influenced by the extent of virus suppression and exposure

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Background:Virus-specific CD4 T cells play a critical role in antiviral immunity. HIV-1-specific CD4 T cells in chronically infected adults are mostly composed of IFN-γ-secreting cells, whereas a selective defect in IL-2-secreting CD4 T cells has been demonstrated. HIV-1-specific IL-2-secreting CD4 T cells are key components of effective immunity.Objective:To determine the function of HIV-1-specific CD4 T cells in HIV-1 vertically infected children after antiretroviral treatment (ART).Design:Twenty-three vertically HIV-infected children treated with ART for an extended period (mean 7 years) were retrospectively studied.Methods:The function of HIV-1-specific CD4 T cells was determined by their ability to secrete IL-2 and IFN-γ after stimulation with HIV-1 p55 gag protein using polychromatic flow cytometry.Results:Substantial differences in the patterns of CD4 T-cell responses were associated with different conditions of response to ART. Interestingly, children with suppression of viraemia below 50 HIV-1-RNA copies/ml of plasma for at least 2 years showed dominant IL-2 CD4 T-cell responses; children with viraemia below 50 copies but experiencing transient blips of viraemia showed polyfunctional (IL-2 plus IFN-γ) CD4 T-cell responses; children with uncontrolled high viraemia levels had dominant IFN-γ CD4 T-cell responses. Furthermore, the total frequency of HIV-1-specific CD4 T cells including IL-2 and IFN-γ-secreting cells was significantly higher compared with HIV-infected adults with chronic infection.Conclusion:The higher frequency of HIV-1-specific CD4 T cells in children compared with adults and the recovery of IL-2-secreting CD4 T cells after successful ART-mediated suppression of virus replication indicate a greater capacity of immune restoration in children than adults.

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