Activated Vγ9Vδ2 T Cells Trigger Granulocyte Functions via MCP-2 Release

Agrati, Chiara; Cimini, Eleonora; Sacchi, Alessandra; Bordoni, Veronica; Gioia, Cristiana; Casetti, Rita; Turchi, Federica; Tripodi, Marco; Martini, Federico

doi:10.4049/jimmunol.182.1.522

Cited by 35 publications

(36 citation statements)

References 42 publications

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“…The observation that neutrophil counts were not affected by CD8 ϩ lymphocyte depletion suggests that the observed decrease in defensin expression reflects a system-wide transcriptional repression. Recent work has demonstrated that ␥␦ T cells are able to modulate the production of ␣-defensins in granulocytes (60) and ␤-defensins in epithelial cells (61). A few studies have reported that CD3 Ϫ CD8 ϩ cells (NK and ␥␦ T cells) produce defensins, and while we failed to detect significant levels of defensin mRNA, it remains formally possible that a portion of the observed decrease in defensin expression is in part related to their depletion (62)(63)(64).…”

Section: Microarray Analysis Of In Vivo Cd8contrasting

confidence: 51%

Transcriptional Profiling of Experimental CD8⁺Lymphocyte Depletion in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239

Bosinger

Jochems

Folkner

et al. 2013

J Virol

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c CD8 ؉ T cells inhibit virus replication in SIV-infected rhesus macaques. However, it is unclear to what extent the viral suppression mediated by CD8؉ T cells reflects direct killing of infected cells as opposed to indirect, noncytolytic mechanisms. In this study, we used functional genomics to investigate noncytolytic mechanisms of in vivo viral suppression mediated by CD8؉ lymphocytes. Eight chronically SIVmac239-infected rhesus macaques underwent CD8؉ lymphocyte depletion, and RNA from whole blood was obtained prior to depletion, during the nadir of CD8 ؉ cell depletion, and after CD8 ؉ lymphocyte numbers had rebounded. We observed significant downregulation of the expression of genes encoding factors that can suppress SIV replication, including the CCR5-binding chemokine CCL5/RANTES and CCL4 and several members of the tripartite motif-containing (TRIM) family. Surprisingly, we also noted a strong, widespread downregulation of ␣-and -defensins with anti-HIV activity, which are not expressed by CD8 ؉ T cells. After cessation of depleting antibody treatment, we observed induction of a transcriptional signature indicative of B lymphocyte activation. Validation experiments demonstrated that animals during this period had elevated levels of B cells coupled with higher expression of the proliferative marker Ki67, indicating that CD8 ؉ depletion triggered a potent expansion of B cell numbers. Collectively, these data identify antiviral pathways perturbed by in vivo CD8؉ T cell depletion that may contribute to noncytolytic control of SIV replication.

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Section: Microarray Analysis Of In Vivo Cd8contrasting

confidence: 51%

Transcriptional Profiling of Experimental CD8⁺Lymphocyte Depletion in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239

Bosinger

Jochems

Folkner

et al. 2013

J Virol

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“…Among mucosal immune cells, γδ T-cells are known to be able to perform an antiviral activity by exerting a cytolytic activity, by releasing antiviral soluble factors [29,30] and by orchestrating the deployment of specific immune response [31,32]. Moreover, γδ T-cells are known to be specifically impaired during HIV infection [13,14,17,19].…”

Section: Discussionmentioning

confidence: 99%

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

Cimini

Agrati²,

D’Offizi

et al. 2015

PLoS ONE

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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.

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“…In contrast, in a prior study assessing the chemotaxis of human neutrophils, CCL8 synergistically enhanced neutrophil chemotaxis in the setting of low doses of IL-8 (85). Using a model of human ␥␦ T cell-monocyte coculture to study the effect of ␥␦ T cell activation on granulocyte function, another group showed that CCL8 promotes neutrophil degranulation (86). Future studies will assess the ability of CCL8 to promote neutrophil recruitment, degranulation, and phagocytosis.…”

Section: Fig 11mentioning

confidence: 96%

Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner

et al. 2014

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f The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity.

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Activated Vγ9Vδ2 T Cells Trigger Granulocyte Functions via MCP-2 Release

Cited by 35 publications

References 42 publications

Transcriptional Profiling of Experimental CD8⁺Lymphocyte Depletion in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239

Transcriptional Profiling of Experimental CD8⁺Lymphocyte Depletion in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239

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

Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner

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Activated Vγ9Vδ2 T Cells Trigger Granulocyte Functions via MCP-2 Release

Cited by 35 publications

References 42 publications

Transcriptional Profiling of Experimental CD8+Lymphocyte Depletion in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239

Transcriptional Profiling of Experimental CD8+Lymphocyte Depletion in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239

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

Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner

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Product

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Transcriptional Profiling of Experimental CD8⁺Lymphocyte Depletion in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239

Transcriptional Profiling of Experimental CD8⁺Lymphocyte Depletion in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239