Abstract
T regulatory cells (Tregs) are a key component of the immune system, which maintain a delicate balance between overactive responses and immunosuppression. As such, Treg deficiencies are linked to autoimmune disorders and alter the immune control of pathogens. In HIV infection, Tregs play major roles, both beneficial and detrimental. They regulate the immune system such that inflammation and spread of virus through activated T cells is suppressed. However, suppression of immune activation also limits viral clearance and promotes reservoir formation. Tregs can be directly targeted by HIV, thereby harboring a fraction of the viral reservoir. The vital role of Tregs in the pathogenesis and control of HIV makes them a subject of interest for manipulation in the search of an HIV cure. Here, we discuss the origin and generation, homeostasis, and functions of Tregs, particularly their roles and effects in HIV infection. We also present various Treg manipulation strategies, including Treg depletion techniques and interventions that alter Treg function, which may be used in different cure strategies, to simultaneously boost HIV-specific immune responses and induce reactivation of the latent virus.
Highlights
The human immune system walks a fine line between protection from pathogens and self-reactivity
It was shown that T regulatory cells (Tregs) form two distinct populations, the CD44lo CD62Lhi central Tregs, which actively recir culate through lymphoid organs and are sustained by paracrine IL-2, and the CD44hi CD62Llo CCR7lo effector Tregs, which are not found in the lymphoid tissue, do not require IL-2, and are instead maintained by inducible costimulator (ICOS) [71]
Additional support for the role of Tregs in acute infection was obtained by Cecchinato et al who showed that CTLA-4 blockade early during the acute infection was detrimental to Rhesus macaques (RMs), resulting in increased viral replication and decreased responsiveness to ART [154]
Summary
In HIV infection, Tregs play major roles, both beneficial and detrimental. They regulate the immune system such that inflammation and spread of virus through activated T cells is suppressed. Suppression of immune activation limits viral clearance and promotes reservoir formation. Tregs can be directly targeted by HIV, thereby harboring a fraction of the viral reservoir. We discuss the origin and generation, homeostasis, and functions of Tregs, their roles and effects in HIV infection. We present various Treg manipulation strategies, including Treg depletion techniques and interventions that alter Treg function, which may be used in different cure strategies, to simultaneously boost HIV-specific immune responses and induce reactivation of the latent virus
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