Preferential Loss of Th17 T‐cells at Mucosal Sites Predicts AIDS Progression in Simian Immunodeficiency Virus‐Infected Macaques

Abstract

Depletion of CD4+ T‐cells in the gut is necessary but not sufficient to cause AIDS in animal models, raising the possibility that differential depletion of CD4+ T‐cell subtypes may be important. We found that Th17 cells, a recently identified lineage of effector CD4+ T‐helper interleukin‐17‐secreting cells, express CCR5, are infected in vitro and in vivo, and are preferentially depleted within a few weeks in the pathogenic model of simian immunodeficiency virus (SIVmac251) infection of macaques. Importantly, their frequency is not restored to normal levels over time. We also found that SIVmac251‐infected “elite controllers” maintain normal levels of Th17 T‐cells in all tissues, and that there is a negative correlation between Th17 cell frequency at mucosal sites and plasma virus level, suggesting their importance in HIV/SIV pathogenesis. Because Th17 cells play a central role in innate and adaptive immune response to extracellular bacteria, these data provide a rational explanation for the chronic enteropathy in HIV infection. Thus, therapeutic approaches to incease Th17 numbers and/or function may be of benefit in HIV infection.