The Impaired Response of NK Cells from HIV-infected Progressor Patients to A-class CpG Oligodeoxynucleotides is Largely Dependent of a Decreased Production of IL-12

We have reported that NK cells from HIV-infected progressors showed a markedly lower IFN-gamma production in response to an A-class CpG oligodeoxynucleotide as compared to LTNP subjects and healthy HIV-negative individuals. This functional defect was not related to the number of circulating plasmacytoid dendritic cells, nor to the alpha-interferon secreted. In contrast, defective response correlated negatively with the frequency of myeloid dendritic cells. Furthermore, peripheral blood mononuclear cells from LTNPs as well as those from some healthy HIV-negative donors secreted large amounts of IL-12 in unstimulated cultures and in response to the CpG-ODN whereas, HIV-progressor cells showed impaired responses and low level of spontaneous secretion. The addition of a monoclonal anti-IL-12 reduced the response to the CpG-ODN in a dose-dependent manner. These results suggest that the impaired response of NK cells to the CpG-ODN in HIV-progressors is largely dependent on a decreased production of IL-12.