Regulatory T Cells in HIV Infection: Can Immunotherapy Regulate the Regulator?

Abstract

Regulatory T cells (Tregs) have a dominant role in self-tolerance and control of autoimmune diseases. These cells also play a pivotal role in chronic viral infections and cancer by limiting immune activation and specific immune response. The role of Tregs in HIV pathogenesis remains poorly understood as their function, changes according to the phases of infection. Tregs can suppress anti-HIV specific responses and conversely can have a beneficial role by reducing the deleterious impact of immune activation. We review the frequency, function and homing potential of Tregs in the blood and lymphoid tissues as well as their interaction with dendritic cells in the context of HIV infection. We also examine the new insights generated by recombinant IL-2 and IL-7 clinical trials in HIV-infected adults, including the immunomodulatory effects of Tregs. Based on their detrimental role in limiting anti-HIV responses, we propose Tregs as potential targets for immunotherapeutic strategies aimed at decreasing Tregs frequency and/or immunosuppressive function. However, such approaches require a better understanding of the time upon infection when interfering with Treg function may not cause a deleterious state of hyperimmune activation.

Distinct Tryptophan Catabolism and Th17/Treg Balance in HIV Progressors and Elite Controllers

“…The Th17/Treg balance plays a dominant role in the maintenance of mucosal immunity [9,16]. These cells are derived from common progenitor cells and their differentiation pathways are reciprocally modulated upon immune activation during HIV-1 infection, resulting in bacterial translocation [9,18,20,21].…”

“…Among T-cell subsets, regulatory T-cells (Tregs), play a pivotal role in peripheral tolerance and pathogenesis of cancer and chronic viral infections [16]. Indeed, Tregs were shown to suppress effector T-cells activation and function [17].…”

Regulatory T Cell in Stroke: A New Paradigm for Immune Regulation

“…Particularly, studies reported that FoxP3 + CD25 + CD4 + Tregs are important neuroprotective immunomodulators in stroke, but their contributive effects towards stroke pathophysiology are still controversial [12, 27, 28]. Although many review articles have focused on FoxP3 + CD25 + CD4 + Tregs [9, 29, 30], a new review is necessary for appraising recent research advances in FoxP3 + CD25 + CD4 + Tregs after stroke. The objectives of this review are (1) survey the evidence of the vital roles played by FoxP3 + CD25 + CD4 + Tregs in stroke pathophysiology, (2) discuss further investigations to fully elucidate the precise regulatory mechanisms of FoxP3 + CD25 + CD4 + Tregs in stroke, and (3) evaluate the possible therapeutic application and potential pitfalls of modulating the activity and quantity of FoxP3 + CD25 + CD4 + Tregs in stroke treatment.…”

Caracterização fenotípica e funcional de IFN-DCs derivadas de indivíduos infectados pelo HIV-1.

“…Durante a infecção pelo HIV, a expansão de células Treg poderia ser benéfica por suprimir a ativação generalizada de células T, ou poderia ser prejudicial por suprimir o impacto deletério causado pela ativação de respostas imunes anti-HIV e assim contribuindo com a persistência viral (Chevalier, Weiss, 2013;Jenabian et al, 2012;Sunder et al, 2012). Células dendríticas possuem um papel crucial na resposta imune ao HIV, pois são essenciais na indução de respostas HIV-específicas por meio da ativação de linfócitos T auxiliares CD4+, que uma vez ativados auxiliam as DCs na ativação de linfócitos T citotóxicos CD8+ (CTL) capazes de controlar a replicação viral (Banchereau et al, 2000;Day, Walker, 2003;Hugues, 2004;Letvin, Walker, 2003 Com base nisso, podemos sugerir que em nosso protocolo, a substituição da IL-4 pelo IFN-α, apenas, ainda não seja o suficiente para potencializar a habilidade das MoDCs em promover uma resposta imune antiviral mais eficaz.…”