Primary and Chronic HIV Infection Differently Modulates Mucosal Vδ1 and Vδ2 T-Cells Differentiation Profile and Effector Functions

• Published in: PloS one Vol. 10; no. 6; p. e0129771
• Main Authors: Cimini, Eleonora, Agrati, Chiara, D’Offizi, Gianpiero, Vlassi, Chrysoula, Casetti, Rita, Sacchi, Alessandra, Lionetti, Raffaella, Bordoni, Veronica, Tumino, Nicola, Scognamiglio, Paola, Martini, Federico
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.06.2015; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Blood circulation; Cell Differentiation; Chemokines; Chronic Disease; Chronic infection; Cytotoxicity; Dendritic cells; Differentiation; Effector cells; Exhaustion; Female; Flow cytometry; Gastric cancer; HIV; HIV Infections - immunology; HIV Infections - virology; Human immunodeficiency virus; Humans; Immune system; Immunity; Immunity, Mucosal; Immunology; Infections; Infectious diseases; Laboratories; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Male; Middle Aged; Military technology; Mucosal immunity; Receptors, Antigen, T-Cell, gamma-delta - immunology; Stomach cancer; T cell receptors; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - virology; γ-Interferon; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0129771

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.