Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection

During chronic hiv infection,viral replication is concentrated in secondary lymphoid follicles. cytotoxic cd8 t cells control hiv replication in extrafollicular regions,but not in the follicle. here,we show cxcr5hicd44hicd8 t cells are a regulatory subset differing from conventional cd8 t cells,and constitute the majority of cd8 t cells in the follicle. this subset,cd8 follicular regulatory t cells (cd8 tfr),expand in chronic siv infection,exhibit enhanced expression of tim-3 and il-10,and express less perforin compared to conventional cd8 t cells. cd8 tfr modestly limit hiv replication in follicular helper t cells (tfh),impair tfh il-21 production via tim-3,and inhibit igg production by b cells during ex vivo hiv infection. cd8 tfr induce tfh apoptosis through hla-e,but induce less apoptosis than conventional cd8 t cells. these data demonstrate that a unique regulatory cd8 population exists in follicles that impairs gc function in hiv infection. © 2016 miles et al.