Follicular T-cell subsets in HIV infection

Abstract

Purpose of review-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. Recent findings-B cell follicles are major sites of virus replication and demonstrate significant impairments in 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 development of effective HIV vaccines and cure strategies. Summary-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.

Human immunodeficiency virus dynamics in secondary lymphoid tissues and the evolution of cytotoxic T lymphocyte escape mutants

“…2017 ; Bronnimann, Skinner, and Connick 2018 ; Beck, Veenhuis, and Blankson 2019 ; Li et al. 2019 ; Xu, Ollerton, and Connick 2019 ). The follicular (F) compartments contain follicular CD4 T helper cells with higher permissiveness for viral replication than extrafollicular CD4 T cells and have a high concentration of extracellular virions on the surface of follicular dendritic cells.…”

Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance

“…Decreased adaptive immune responses are a hallmark of progressive lentiviral infection (27)(28)(29)(30)(31)(32)(33). Although the underlying mechanisms are multifactorial, preferential HIV/SIV infection of follicle-resident CD4 ϩ Tfh cells (reviewed in reference 65), loss of pathogen-specific memory CD4 ϩ T cells (66,67), exhaustion of adaptive lymphocytes (68,69), and aberrant inflammation (70) are all described contributors.…”

“…Tfh cells are an important reservoir for HIV/SIV (27)(28)(29)(30)(31)(32)(33), and their predicted infection by SIV in our coinfection model may compromise the generation of ZIKV antibodies. A combination of Tfh loss and ISG-mediated hypoantigenemia may be cumulatively operative in decreasing ZIKV-specific NAbs.…”

“…While this sensitivity to opportunistic infections generally occurs very late after the acquisition of infection, several studies have shown that HIV-infected individuals and SIV-infected rhesus macaques (RMs) mount suboptimal adaptive immune responses to vaccination and viral infections (24)(25)(26)(27). The decreased humoral responses to vaccination, in particular, have been attributed to preferential infection of lymph node follicle-resident T follicular cells, which provide critical help to B cells during the germinal center reaction (27)(28)(29)(30)(31)(32)(33).…”

Human immunodeficiency virus (HIV) dynamics in secondary lymphoid tissues and the evolution of cytotoxic T lymphocyte (CTL) escape mutants

“…The majority of HIV replication occurs in the secondary lymphoid tissues, such as lymph nodes, spleen, or the gut-associated lymphoid tissue (GALT) [1]. Within these tissues, virus replication is concentrated in the B cell follicles, with lower levels of replication observed in the extrafollicular compartments in the absence of antiretroviral therapy [2][3][4][5][6][7][8][9][10][11][12][13]. The follicular compartments contain follicular CD4 T helper cells with higher permissiveness for viral replication than extrafollicular CD4 T cells, and have a high concentration of extracellular virions on the surface of follicular dendritic cells (FDCs).…”