Connick Lab reports novel findings on the roles of follicular regulatory T cells in HIV and SIV disease in Nature Communications
It is known that 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 (TFR) are a recently characterized subset of regulatory T cells that influence the germinal centre response through interactions with follicular helper T cells (TFH).
The Connick laboratory has now reported in Nature Communications (published Oct. 20, 2015) on the expansion of a novel subset of TFRs, in both HIV and SIV infection. Utilizing human and rhesus macaque models, they show the impact of HIV and SIV infection on TFR number and function. They find that TFR 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, TFR exhibit elevated regulatory phenotypes and impair TFH functions during HIV infection. Thus, TFR contribute to inefficient germinal centre responses and inhibit HIV and SIV clearance.
These findings could help explain why HIV-infected individuals have impaired humoral immunity, particularly broadly neutralizing antibodies, and have implications for vaccine development as well as HIV cure strategies.