Background:  Following viral infection, plasmacytoid dendritic cells (pDC) are activated, undergo maturation, and express  new surface markers including CCR7, a homing receptor that facilitates their migration to lymph nodes and facilitates the maturation of myeloid DC and these in turn are critical for T-cell responses. CCR7 is also a marker for central memory CD8 T cells that home to lymph nodes. We tested the hypothesis that a homing defect occurs in progressive HIV disease in perinatally infected children and adolescents on long-term ART.

Methods:  pDC (Lin^–, HLA DR⁺ CD123⁺) were evaluated in whole blood assay by flow cytometry for expression of maturation markers CD83, CD80, homing receptor CCR7, and intracellular cytokines (tumor necrosis factor-alpha [TNF-α] and interferon-alpha [IFN-α]) after short-term stimulation with a TLR7/8 agonist, resiquimod (RSQ) in perinatally HIV-infected children (n = 20). RNA was extracted from peripheral blood mononuclear cells (PBMC) and relative CCR7 mRNA relative expression levels was quantified by real-time polymerase chain reaction (RT-PCR) with the ABI/PRISM 7700 sequence detection system using the comparative threshold cycle (CT) method (2^–ΔΔCT). CD4 and CD8 CCR7 expression was assessed by flow cytometry in cryopreserved samples. Spearman correlation and Kruskal-Wallis test were used as statistical tools.

Results:  pDC CCR7 expression was decreased in patients with poor immunologic response (IR^–) and lack of viral control (VR^–) in comparison to healthy donors, and good immunologic/virologic responders (IR⁺VR⁺). CCR7 expression was independent of IFN-a response. Selective impairment of CCR7 mRNA expression was observed in PBMC of IR^– patients (p = 0.03) compared to IR⁺ patients. The CCR7 mRNA expression levels in PBMC correlated with CD4% (r = 0.6507, p = 0.0047), with inverse correlation to viral load (r = –0.6625, p = 0.0127). CCR7 expression on CD8 T cells was significantly higher in IR⁺ than in IR^– subjects (p = 0.032), there was no difference in the CCR7 expression on CD4 T cells.

Conclusions:  A generalized defect in CCR7 could result in defective homing of DC and other cells of immune system to the lymphnode. Further investigations to decipher the mechanism underlining the CCR7 mRNA expression, are warranted.