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Review
. 2018 Apr 13:9:734.
doi: 10.3389/fimmu.2018.00734. eCollection 2018.

Regulatory T Cells As Potential Targets for HIV Cure Research

Adam J Kleinman  1   2 , Ranjit Sivanandham  1   3 , Ivona Pandrea  1   3   4 , Claire A Chougnet  5 , Cristian Apetrei  1   2   4
Affiliations
Review

Regulatory T Cells As Potential Targets for HIV Cure Research

Adam J Kleinman et al. Front Immunol. .

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.

Keywords: FoxP3; cytotoxic T lymphocytes; human immunodeficiency virus; lymph node; regulatory T cells; simian immunodeficiency virus; virus eradication.

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Figures

Figure 1
Figure 1
Flow chart illustrating the effects of Tregs on the HIV reservoir (A). Tregs can be infected with HIV, thereby contributing to the HIV reservoir. Tregs reverse the activation status of the HIV-infected T cells into resting T cells, further contributing to the reservoir formation. Finally, by suppressing the HIV-specific CD8+ T cells, which would otherwise kill infected cells, Tregs also shape the non-Treg reservoir. Potential effects of Treg depletion on the HIV reservoir (B). Treg depletion obviously result in a reduction of the Treg reservoir through direct killing. Treg depletion also abolish their suppressive effects of the T cells, which may reverse their resting status, become activated and produce and release the virus. Finally, reversion of the suppressive effect of Tregs on HIV-specific CD8+ T cells has the potential to boost their anti-SIV activity, which can also curtail the reservoir.
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