Distortion of memory Vδ2 γδ T cells contributes to immune dysfunction in chronic HIV infection

Li, Zhen; Jiao, Yanmei; Hu, Yu; Cui, Lianxian; Chen, Dexi; Wu, Hao; Zhang, Jianmin; Wang, He

doi:10.1038/cmi.2014.77

Cited by 21 publications

(45 citation statements)

References 48 publications

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“…50 Given early reports that Vd2 T cells lacked expression of CD4 51 and were resistant to direct HIV infection, 52 there has been a strong emphasis on determining the mechanism of peripheral depletion, albeit with little consensus. 32,33 Vd2 depletion is also associated with a reduction of antigen-induced IFNc 46 /TNFa 57 /TGFb 47 production and proliferative/cytotoxic capacity 48,58,59 in the residual Vd2 population. 53 gp120-induced cross-linking of CCR5 and a4b7 on CD4 À Vd2 T cells results in the activation of the p38 caspase pathway and eventual apoptosis, without productive infection of the cell.…”

Section: Progressive Hiv-1 Infection Peripheral Vd2vc9 T Cellsmentioning

confidence: 96%

“…Li and Pauza presented evidence implicating the HIV gp120 binding proteins a4b7 and CCR5 in mediating Vd2 depletion in viremic patients. 32,33,47 Although all Vd2 memory subsets exhibit significant increases in activation during acute and chronic HIV infection, 33,47 T EMRA cells tend to exhibit the highest levels of activation as measured by CD38 expression. To date, this mechanism remains to be confirmed, but analysis of existing data from preclinical studies of a4b7 monoclonal antibody (mAb) blockade 54-56 may provide interesting insights into this phenomenon.…”

Section: Progressive Hiv-1 Infection Peripheral Vd2vc9 T Cellsmentioning

confidence: 99%

“…53 gp120-induced cross-linking of CCR5 and a4b7 on CD4 À Vd2 T cells results in the activation of the p38 caspase pathway and eventual apoptosis, without productive infection of the cell. 33 However, no studies have conclusively demonstrated a causal relationship between memory differentiation or activation and loss of antigen-induced cytokine responses in HIV. An alternative hypothesis suggests that microbial translocation associated with acute HIV infection could drive Vd2 T-cell activation and apoptosis.…”

Section: Progressive Hiv-1 Infection Peripheral Vd2vc9 T Cellsmentioning

confidence: 99%

“…10 However, they have been observed to expand in the blood in patients with cytomegalovirus infection, CD4 T-cell deficiency and B-cell leukaemia. 29 Multiple reports have since described an inversion of the typical Vd2:Vd1 T-cell ratio in the peripheral blood of HIV-infected/AIDS patients, [30][31][32][33] which was quickly determined to represent an increase in Vd1 T-cell frequency 30,[32][33][34][35][36][37][38][39][40][41][42][43][44] and a depletion of Vd2Vc9 T cells. In 2017, an estimated 36.9 million people were currently infected with the virus of which 1.8 million were children under the age of 15.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13][14][15] HIV-1 (herein referred to as HIV) infection still remains one of the most challenging health issues worldwide. [31][32][33]35,38,[41][42][43][44][45][46][47][48] Subsequent investigations have focused on the mechanisms behind this expansion/depletion, as well as the relationship of cd T subsets to HIV disease progression. Despite increasing awareness of the disease and improved access to antiretroviral therapy (ART), approximately 5000 individuals become newly infected every day.…”

Section: Introductionmentioning

confidence: 99%

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γδ T‐cell responses during HIV infection and antiretroviral therapy

Juno

Eriksson

2019

Clin & Trans Imm

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HIV infection is associated with a rapid and sustained inversion of the Vδ1:Vδ2 T‐cell ratio in peripheral blood. Studies of antiretroviral therapy (ART)‐treated cohorts suggest that ART is insufficient to reconstitute either the frequency or function of the γδ T‐cell subset. Recent advances are now beginning to shed light on the relationship between microbial translocation, chronic inflammation, immune ageing and γδ T‐cell immunology. Here, we review the impact of acute, chronic untreated and treated HIV infection on circulating and mucosal γδ T‐cell subsets and highlight novel approaches to harness γδ T cells as components of anti‐HIV immunotherapy.

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Section: Progressive Hiv-1 Infection Peripheral Vd2vc9 T Cellsmentioning

confidence: 96%

Section: Progressive Hiv-1 Infection Peripheral Vd2vc9 T Cellsmentioning

confidence: 99%

Section: Progressive Hiv-1 Infection Peripheral Vd2vc9 T Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

γδ T‐cell responses during HIV infection and antiretroviral therapy

Juno

Eriksson

2019

Clin & Trans Imm

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γδ T cells mediate robust anti‐HIV functions during antiretroviral therapy regardless of immune checkpoint expression

Field,

Wragg,

Kent

et al. 2024

Clin & Trans Imm

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ObjectivesAlthough antiretroviral therapy (ART) efficiently suppresses HIV viral load, immune dysregulation and dysfunction persist in people living with HIV (PLWH). γδ T cells are functionally impaired during untreated HIV infection, but the extent to which they are reconstituted upon ART is currently unclear.MethodsUtilising a cohort of ART‐treated PLWH, we assessed the frequency and phenotype, characterised in vitro functional responses and defined the impact of immune checkpoint marker expression on effector functions of both Vδ1 and Vδ2 T cells. We additionally explore the in vitro expansion of Vδ2 T cells from PLWH on ART and the mechanisms by which such expanded cells may sense and kill HIV‐infected targets.ResultsA matured NK cell‐like phenotype was observed for Vδ1 T cells among 25 ART‐treated individuals (PLWH/ART) studied compared to 17 HIV‐uninfected controls, with heightened expression of 2B4, CD160, TIGIT and Tim‐3. Despite persistent phenotypic perturbations, Vδ1 T cells from PLWH/ART exhibited strong CD16‐mediated activation and degranulation, which were suppressed upon Tim‐3 and TIGIT crosslinking. Vδ2 T cell degranulation responses to the phosphoantigen (E)‐4‐hydroxy‐3‐methyl‐but‐2‐enyl pyrophosphate at concentrations up to 2 ng mL−1 were significantly impaired in an immune checkpoint‐independent manner among ART‐treated participants. Nonetheless, expanded Vδ2 T cells from PLWH/ART retained potent anti‐HIV effector functions, with the NKG2D receptor contributing substantially to the elimination of infected cells.ConclusionOur findings highlight that although significant perturbations remain within the γδ T cell compartment throughout ART‐treated HIV, both subsets retain the capacity for robust anti‐HIV effector functions.

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Evolved to protect, designed to destroy: IL‐17‐producing γδ T cells in infection, inflammation, and cancer

Agerholm

Bekiaris

2021

Eur J Immunol

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T cells of the gamma delta (γδ) lineage are evolutionary conserved from jawless to cartilaginous and bony fish to mammals and represent the "swiss army knife" of the immune system capable of antigen-dependent or independent responses, memory, antigen presentation, regulation of other lymphocytes, tissue homeostasis, and mucosal barrier maintenance, to list a few. Over the last 10 years, γδ T cells that produce the cytokine IL-17 (γδT17) have taken a leading position in our understanding of how our immune system battles infection, inflicts tissue damage during inflammation, and gets rewired by the tumor microenvironment. A lot of what we know about γδT17 cells stems from mouse models, however, increasing evidence implicates these cells in numerous human diseases. Herein, we aim to give an overview of the most common mouse models that have been used to study the role of γδT17 cells in infection, inflammation, and cancer, while at the same time we will evaluate evidence for their importance in humans. We hope and believe that in the next 10 years, means to take advantage of the protective and destructive properties of γδ T and in particular γδT17 cells will be part of our standard immunotherapy toolkit.

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Distortion of memory Vδ2 γδ T cells contributes to immune dysfunction in chronic HIV infection

Cited by 21 publications

References 48 publications

γδ T‐cell responses during HIV infection and antiretroviral therapy

γδ T‐cell responses during HIV infection and antiretroviral therapy

γδ T cells mediate robust anti‐HIV functions during antiretroviral therapy regardless of immune checkpoint expression

Evolved to protect, designed to destroy: IL‐17‐producing γδ T cells in infection, inflammation, and cancer

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