Differentiation and Function of Follicular CD8 T Cells During Human Immunodeficiency Virus Infection

Minglu Xiao, Xiangyu Chen, Ran He, Lilin Ye

The combination antiretroviral therapeutic (cART) regime effectively suppresses human immunodeficiency virus (HIV) replication and prevents progression to acquired immunodeficiency diseases. However, cART is not a cure, and viral rebound will occur immediately after treatment is interrupted largely due to the long-term presence of an HIV reservoir that is composed of latently infected target cells that maintain a quiescent state or persistently produce infectious viruses. CD4 T cells that reside in B-cell follicles within lymphoid tissues, called follicular helper T cells (TFH), have been identified as a major HIV reservoir. Due to their specialized anatomical structure, HIV-specific CD8 T cells are largely insulated from this TFH reservoir. It is increasingly clear that the elimination of TFH reservoirs is a key step toward a functional cure for HIV infection. Recently, several studies have suggested that a fraction of HIV-specific CD8 T cells can differentiate into a CXCR5-expressing subset, which are able to migrate into B-cell follicles and inhibit viral replication. In this review, we discuss the differentiation and functions of this newly identified CD8 T-cell subset and propose potential strategies for purging TFH HIV reservoirs by utilizing this unique population.