Impaired CCR7 Expression on Plasmacytoid Dendritic Cells in HIV Infected Children on HAART With Virologic Failure

Background

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.

Results

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.

Conclusion

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.