Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART

Abstract

Abstract Recent evidence indicates that regulatory T cells (Tregs) play an important role in HIV infection. However, although the gastrointestinal mucosa is a key compartment in HIV disease, no data on mucosal Tregs in HIV infection are available. In this study, we compared the frequency of Tregs 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. Tregs 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 Tregs 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 Tregs was not increased, and their frequency was only slightly elevated. In norovirus infection, frequency of mucosal Tregs in the CD4+ T-cell subset was not elevated. The high increase in count and frequency of mucosal Tregs seems to be a characteristic feature of untreated HIV infection, suggesting a significant contribution of Tregs 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.