CD8+ T-Cell Response to HIV Infection in the Era of Antiretroviral Therapy

Abstract

Although the combined antiretroviral therapy (cART) has decreased the deaths associated with the immune deficiency acquired syndrome (AIDS), non-AIDS conditions have emerged as an important cause of morbidity and mortality in HIV-infected patients under suppressive cART. Since these conditions are associated with a persistent inflammatory and immune activation state, major efforts are currently made to improve the immune reconstitution. CD8 + T-cells are critical in the natural and cART-induced control of viral replication; however, CD8 + T-cells are highly affected by the persistent immune activation and exhaustion state driven by the increased antigenic and inflammatory burden during HIV infection, inducing phenotypic and functional alterations, and hampering their antiviral response. Several CD8 + T-cell subsets, such as interleukin-17-producing and follicular CXCR5 + CD8 + T-cells, could play a particular role during HIV infection by promoting the gut barrier integrity, and exerting viral control in lymphoid follicles, respectively. Here, we discuss the role of CD8 + T-cells and some of their subpopulations during HIV infection in the context of cART-induced viral suppression, focusing on current challenges and alternatives for reaching complete reconstitution of CD8 + T-cells antiviral function. We also address the potential usefulness of CD8 + T-cell features to identify patients who will reach immune reconstitution or have a higher risk for developing non-AIDS conditions. Finally, we examine the therapeutic potential of CD8 + T-cells for HIV cure strategies.

Induced Pluripotent Stem Cells Provide an Unlimited T-cell Source for CAR-T cell Development and A Potential Source for Off-the-shelf Products

“…This labor-intensive generation of T-cell lines from the patients consumes time and may not be applied to those who have insufficient T cells. These include HIV-infected or T cell leukemia patients and leukemia patients with relapse after allogeneic hematopoietic cell transplantation and those the use of allogeneic donor lymphocyte infusions is challenging [103][104][105][106]. Having a rapid access to unlimited T-cell sources with optimized physiological features would remarkably improve the success of genetically engineered-T cells.…”

The role of CD8 T cells in controlling HIV beyond the antigen‐specific face

“…For instance, activated CD8 T cells release the cytotoxic molecules perforin and granzyme B through degranulation. The degranulation process can be detected via the expression of lysosome-associated membrane glycoproteins, such as CD107a [42]. Activated CD8 T cells also secrete antiviral cytokines, including IFN-c, tumour necrosis factor-a (TNF-a) and some chemokines [42].…”

Epidemiology of multimorbidity among people living with HIV in sub-Saharan Africa: a systematic review protocol

“…[7][8][9] Unfortunately, emerging non-acquired immune-deficiency syndrome (non-AIDS) conditions in HIV-infected patients treated with highly active ART has greatly affected progress made in the reduction of HIV-related deaths. 10 The implication of these emerging non-AIDS conditions is a devastating increase in the burden of multimorbidity ranging from chronic noncommunicable diseases (NCD) such as Strengths and limitations of this study ► Reporting incident, prevalent estimates and trajectories of the multimorbidity burden among people living with HIV across different sociodemographic settings in sub-Saharan Africa epidemic will provide requisite evidence to inform clinical thinking and practice. ► Findings may be integrated into non-communicable diseases surveillance programmes, health systems and delivery for patient-centric prevention and control services of cardiometabolic diseases by national HIV care programmes.…”