Abstract
Gut-associated immune system has been identified as a major battlefield during the early phases of HIV infection. γδ T-cells, deeply affected in number and function after HIV infection, are able to act as a first line of defence against invading pathogens by producing antiviral soluble factors and by killing infected cells. Despite the relevant role in mucosal immunity, few data are available on gut-associated γδ T-cells during HIV infection. Aim of this work was to evaluate how primary (P-HIV) and chronic (C-HIV) HIV infection affects differentiation profile and functionality of circulating and gut-associated Vδ1 and Vδ2 T-cells. In particular, circulating and mucosal cells were isolated from respectively whole blood and residual gut samples from HIV-infected subjects with primary and chronic infection and from healthy donors (HD). Differentiation profile and functionality were analyzed by multiparametric flow cytometry. P-HIV and C-HIV were characterized by an increase in the frequency of effector Vδ1-T cells both in circulating and mucosal compartments. Moreover, during P-HIV mucosal Vδ1 T-cells expressed high levels of CD107a, suggesting a good effector cytotoxic capability of these cells in the early phase of infection that was lost in C-HIV. P-HIV induced an increase in circulating effector Vδ2 T-cells in comparison to C-HIV and HD. Notably, P-HIV as well as HD were characterized by the ability of mucosal Vδ2 T-cells to spontaneously produce IFN-γ that was lost in C-HIV. Altogether, our data showed for the first time a functional capability of mucosal Vδ1 and Vδ2 T-cells during P-HIV that was lost in C-HIV, suggesting exhaustion mechanisms induced by persistent stimulation.
Highlights
A hallmark of HIV infection is the early, dramatic and irreversible impairment of mucosal CD4 T-cells, in gut lymphoid tissue enclaves [1,2]
To study whether primary (P-HIV) and chronic (C-HIV) HIV infection may affect circulating and mucosal γδ T-cells, the frequency and differentiation profile of Vδ1 and Vδ2 T-cells were analysed in healthy donors (HD), P-HIV and C-HIV in two different compartments: i) peripheral blood and ii) gut tissue
In the circulating compartment (Fig 1, Panels A-B), P-HIV and C-HIV were associated to a significant increase of Vδ1 T-cells (p
Summary
A hallmark of HIV infection is the early, dramatic and irreversible impairment of mucosal CD4 T-cells, in gut lymphoid tissue enclaves [1,2]. The innate mucosal immune system represents a key sentinel acting in the early phase of infections by inhibiting microbial replication and by orchestrating the subsequent adaptive immune response. In this context, the ability of γδ T-cells to respond to stress-antigens or phosphoantigens [7] highlights their possible key role in fighting invading pathogens through broad antiviral mechanisms [8]. Many experimental evidences suggest a direct role of circulating Vδ2 T-cells during HIV disease They may exert a direct anti-HIV role by secreting chemokines competing for HIV entry co-receptors as well as other soluble antiviral factors, and by killing infected cells by cytotoxic natural killer-like mechanisms [13]. A persistent functional impairment of Vδ2 T-cells was observed in chronically HIV-infected patients, probably due to the induction of cellular exhaustion or anergy [17,18,19]
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