Background:  Reduced mortality rate of HIV-1 patients co-infected with the GB virus C (GBV-C, formerly known as hepatitis G virus) has been shown previously. These patients have lower viral load and increased CD4 counts. The mechanisms for this beneficial effect remain unclear. Plasmacytoid dendritic cells (pDC) are the major producers of interferon-alpha (IFN-α) and also stimulate T cells in response to viral infection. Reduced pDC number and impaired function has been reported in HIV. However, this impairment of pDC can be restored by ART. We investigated the role of pDC in the beneficial effect of GBV-C in HIV-1-infected patients.

Methods:  Freshly isolated or peripheral blood mononuclear cells (PBMC) stimulated for 24 hours with dinucleotide (CpG) were analyzed by multicolor flow cytometry using a panel of antibodies characteristic for pDC. Frequency and phenotype of pDC were determined by gating on lin^– CD123⁺ HLA DR⁺ BDCA-4⁺ cells.

Results:  Freshly analyzed pDC were positive for CD40, CD83, and CD86. The percentage of pDC expressing CD40 and CD83 was significantly higher in GBV-C co-infected HIV-1 patients:  8.2±1.75% (n = 7 GBV-C⁺) vs 1.08%±0.35% (n = 5 GBV-C^–) for CD40 (p = 0.0079), and 5.37±0.88% (n = 7 GBV-C⁺) vs 2.04±0.58% (n = 5 GBV-C^–) for CD83 (p = 0.017). The mean fluorescence intensity was the same in both groups for CD40, CD83, and CD86. Stimulation in vitro with CpG resulted in comparable expression of the analyzed markers.

Conclusions:  HIV-1 patients co-infected with GBV-C have a higher percentage of pDC expressing CD40 and CD83. This significant difference might contribute to more effective pDC/effector cell interactions to control HIV-1. We are analyzing functional properties of pDCs in GBV-C co-infected and non-co-infected HIV-1 patients to investigate their contribution in HIV-1 pathogenesis.