Cellule dendritiche e patogenesi indotta da HIV: ruolo svolto nell'induzione di citochine TH2-like

Dendritic cells (DC) are professional antigen presenting cells that play a central role in the induction and regulation of immune response towards microbes. In the present study, the capacity of monocytes isolated from HIV+ Caucasian and African patients to differentiate into fully mature DC (MoDC) was evaluated. Moreover the ability of MoDC to induce an HIV specific immune response was investigated. We show that monocytes isolated from HIV infected patients at different stage of the disease are able to differentiate into MoDC in the presence of GM-CSF and IL-4. However, MoDC from 30% of Caucasian and 45% of African patients did not express CD1a molecule on their membrane giving rise to an homogeneus population CD11c+ CD1a-. We observed that the presence of the CD11c+ CD1a- population correlates with the higher percentage of HIV-specific CD4+ T cells producing IL-4. Moreover, in contrast to CD11c+ CD1a+, the CD11c+ CD1a- MoDC produce IL-10 and not IL-12 and when cultured with naive T cells induce a Th2-like polarisation. We found that patients giving rise the CD11c+ CD1a- have a lower CD4 T cell count and higher viral load compared with patients giving rise CD11c+ CD1a+ MoDC. These results suggest that the CD11c+ CD1a- MoDC phenotype correlates with a shift towards a Th2-like immune response and the progression of the disease. Furthermore, we evaluated the maturation state of the peripheral blood DC, observing that plasmacytoid DC from HIV patients express higher level of CD86 compared with healthy donors, suggesting an activated state of that population. Moreover, in HIV patients we found a direct correlation between the expression of CD86 and the viral load, indicating a role of DC in the chronic activation of the immune system associated with the lack of control of the infection.