Mucosal but not peripheral FOYP3+ regulatory T cells are highly increased in untreated HIV infection and nonnalize after suppressive HAART

Recent evidence indicates that regulatory T cells (T-regs) play an important role in HIV infection. However, although the gastrointestinal mucosa is a key compartment in HIV disease, no data on mucosal T-regs in HIV infection are available. In this study, we compared the frequency of T-regs in duodenal mucosa and peripheral blood (PB) of 13 treatment-naive and 13 suppressively treated HIV-infected patients with that of 6 patients with norovirus infection and 12 healthy controls. T-regs were quantified by immunohistochemistry (CD3/FOXP3) and further characterized (CD25, CTLA-4, GITR) by immunohistochemistry, immunofluorescence, and fluorescence-activated cell sorting (FACS). Both the frequency and the absolute count of mucosal T-regs were highly increased in untreated HIV patients but were normal in treated HIV patients. In contrast, in peripheral blood of HIV patients, the absolute number of T-regs was not increased, and their frequency was only slightly elevated. In norovirus infection, frequency of mucosal T-regs in the CD4(+) T-cell subset was not elevated. The high increase in count and frequency of mucosal T-regs seems to be a characteristic feature of untreated HIV infection, suggesting a significant contribution of T-regs to the pathogenesis of HIV disease. Their role may be 2-edged: attenuating HIV-induced immune hyperactivation while suppressing the immune response to HIV and mucosal pathogens.