Follicular T-cell subsets in HIV infection: recent advances in pathogenesis research

T cells within B-cell follicles of secondary lymphoid tissues play key roles in HIV immunopathogenesis. This review highlights recent findings and identifies gaps in current knowledge.

B-cell follicles are major sites of virus replication and demonstrate significant impairments in the generation of humoral immunity in HIV infection. Follicular T helper cells (Tfh), follicular T regulatory cells (Tfr) and follicular CD8 T cells (fCD8) play key roles in HIV immunopathogenesis. Tfh and more recently Tfr are highly permissive to HIV, and may serve as reservoirs of HIV in treated infection. Virus-specific CD8 T cells are less abundant in B-cell follicles than extrafollicular regions, but their effector mechanisms remain an area of significant controversy. Impairments in Tfh likely contribute to impaired humoral immunity and potential mechanisms include B-cell counter-regulatory mechanisms, Tfr suppression and diminished repertoire breadth. A better understanding of the roles of Tfh, Tfr and fCD8 in HIV immunopathogenesis is critical to the development of effective HIV vaccines and cure strategies.

Tfh, Tfr and fCD8 contribute to HIV persistence and impaired humoral immunity. A better understanding of their roles could facilitate vaccine development and HIV cure strategies.