Plasmacytoid dendritic cells (pDCs) have been related with HIV spontaneous control. However, a deregulation mainly consisting in an aberrant IFN-I production lead to an inflammatory environment that could enhance HIV pathogenesis. It has been communicated that HIV provokes alteration in phenotype and location of CD8 T-cells within lymph nodes (LN). In a mouse model, a cooperative activity between pDCs and XCR1 dendritic cells (DCs) in order to effectively antigen cross-priming to CD8+T cells has been reported. However, the phenotype, function of pDCs and its interaction with other cell types in lymphoid tissues in relation with HIV-disease outcomes remain largely unknown.
Seven inguinal LN samples prior to antiretroviral onset were obtained from HIV-infected patients. PBMCs were obtained at the same time point of LN biopsies. A comprehensive analysis of DCs, pDCs and T-cells was performed by deep immunophenotyping using multiparametric flow cytometry.
pDCs levels were inversely correlated with viral load (VL) both in PBMCs and LNs (r=-0.893; p=0.007 and r=-0.9; p=0.037, respectively). Alternatively, VL positively correlated with exhausted pDCs in LN, assessed by PDL-1 expression (r=0.829; p=0.042). Indeed, we found a strong positive correlation between the frequency of pDCs in PBMCs and pDCs in LN (r>0.9, p=0.016). Interestingly, associations between pDCs survival and CD141 mDCs and frequency of follicular CD8 (fCD8) T-cells within LN were presented. The more frequency of CD141 mDCs was present in LN, the less pDCs exhibiting an early stage of apoptosis and the less frequency of fCD8 T-cells were present (r=-0.829, p=0.042 and r=- 0.886, p=0.019, respectively). Furthermore, we found a strong correlation between the percentage of pDCs expressing pDL1 and the levels of follicular CD8+T cells PD1+ (r=0.943, p=0.005). Of note, this correlation was not present neither between the levels of pDCs PD1+ and non-follicular CD8+T cell levels nor with other myeloid dendritic cells expressing PDL1.
We explored a pDCs crosstalk with CD141+mDC and fCD8+T-cells, and its relation with fCD8 T-cell exhaustion in LNs of HIV-infected patients. This pathway may be a drug target that may enhance HIV-specific response within LNs, allowing the development of HIV curative strategies.