TFH in HIV Latency and as Sources of Replication-Competent Virus

Abstract

During untreated disease, HIV replication is concentrated within T follicular helper cells (TFH). Heightened permissiveness, the presence of highly infectious virions on follicular dendritic cells (FDCs), low frequencies of virus-specific cytotoxic T lymphocytes (CTLs) in B cell follicles, expansions in TFH, and TFH dysfunction, all likely promote replication in TFH. Limited data suggest that memory TFH play a role in the latent or subclinical reservoir of HIV during antiretroviral therapy (ART), potentially for many of the same reasons. A better understanding of the role of memory TFH and FDC-bound virions in promoting recrudescent viremia in the setting of ART cessation is essential. Studies that target follicular virus reservoirs are needed to determine their role in HIV latency and to suggest successful cure strategies.

Keywords: HIV-1; T follicular helper cells; follicular dendritic cell; latency.

Figure 1. Model of T_FH Accumulation in Chronic, Untreated HIV Infection

HIV-specific CTL recognize and kill virus producing T cells (HIV+ T cell) in the extrafollicular zone (1), but are found in low numbers within the follicle due to low CXCR5 expression (2). Within the follicle, T follicular helper cells (T_FH) receive both activation signals and infectious HIV from interactions with follicular dendritic cells (FDC) (3). T_FH, including HIV-producing T_FH (HIV+), accumulate within the follicle (4).