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


METHODS
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-gamma 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-gamma) CD4 T-cell responses; children with uncontrolled high viraemia levels had dominant IFN-gamma CD4 T-cell responses. Furthermore, the total frequency of HIV-1-specific CD4 T cells including IL-2 and IFN-gamma-secreting cells was significantly higher compared with HIV-infected adults with chronic infection.


CONCLUSIONS
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.
Correa
Rafael
R
Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
Harari
Alexandre
A
Vallelian
Florence
F
Resino
Salvador
S
Munoz-Fernandez
M Angeles
MA
Pantaleo
Giuseppe
G
D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology; D008297:Male; D014766:Viremia / Q000188:drug therapy / Q000276:immunology
D019380:Anti-HIV Agents; D007376:Interleukin-2; D007371:Interferon-gamma