Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection

Human and simian immunodeficiency viruses (HIV and SIV) exploit follicular lymphoid regions by establishing high levels of viral replication and dysregulating humoral immunity. Follicular regulatory T cells (T(FR)) are a recently characterized subset of lymphocytes that influence the germinal centre response through interactions with follicular helper T cells (T(FH)). Here, utilizing both human and rhesus macaque models, we show the impact of HIV and SIV infection on T(FR) number and function. We find that T(FR) proportionately and numerically expand during infection through mechanisms involving viral entry and replication, TGF-β signalling, low apoptosis rates and the presence of regulatory dendritic cells. Further, T(FR) exhibit elevated regulatory phenotypes and impair T(FH) functions during HIV infection. Thus, T(FR) contribute to inefficient germinal centre responses and inhibit HIV and SIV clearance.