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Impaired CCR7 Expression on Plasmacytoid Dendritic Cells in HIV Infected Children on HAART With Virologic Failure
Retrovirologyvolume 2, Article number: P28 (2005)
Defects of myeloid (m) DC and plasmacytoid (p) DC are well established in HIV infection. Studies in children and adolescents are limited, and have focused mainly on IFN-α function of pDCs.
Materials and methods
Patients with perinatal HIV infection (n = 19, ages 11–18 yr, on HAART) were classified as immunologic responders (IR+; CD4>25%), and virologic responders (VR; plasma HIV RNA < 400 copies/mL). mDC (Lin-, HLA DR+CD11c+) and pDC (Lin-, HLA DR+ CD11c-) were evaluated in a novel whole blood assay by flow cytometry for expression of maturation markers CD83, CD80, homing receptor CCR7 and intracellular cytokines (TNF-α and IFN-α) after short-term stimulation with a TLR7/8 agonist, resiquimod.
CCR7 expression was markedly reduced in pDC of IR-VR- subjects in comparison to IRVR patients (mean 5.6% vs 43.3%). Levels of CCR7 were intermediate (mean 29.8%) in the IR+VR- group, and were almost absent in two patients with VL>100,000 copies who had a markedly reduced IFN-α production in pDC. CD83, CD80, and TNF-a were expressed in all patients and were more pronounced in mDC than in pDC.
The most striking finding was a reduced expression of CCR7, and is indicative of a defect in homing of the plasmacytoid DC to lymph nodes in HIV infected children who have ongoing active viral replication and poor immunologic control in spite of HAART.