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Potential Role of V?2⁺ ?? T Cells in Regulation of Immune Activation in Primary HIV Infection.

ABSTRACT: Although conventional regulatory T cells (Tregs) are sufficient in controlling low residual T-cell activation in ART-treated patients, they are not efficient in controlling exaggerated immune activation associated with high levels of HIV replication in primary HIV infection (PHI). Our previous data suggested that double negative (DN) T cells including mainly ?? DN T cells play a role in the control of immune activation in PHI. Since ?? T cells are capable of exerting regulatory functions, we investigated their implication as Tregs in PHI as well as chronic HIV infection (CHI). In a cross-sectional study of 58 HIV-infected patients, in the primary and the chronic phase either ART-treated or untreated (UT), we analyzed phenotype and cytokine production of ?? T cells using flow cytometry. Cytokine production was assessed following in vitro stimulation with isopentenyl pyrophosphate or plate-bound anti-CD3/anti-CD28 monoclonal antibodies. We found that the proportion of ?? T cells negatively correlated with CD8 T-cell activation in PHI patients. Furthermore, we found that in these patients, the V?2 receptor bearing (V?2⁺) ?? T cells were strongly activated, exhibited low terminal differentiation, and produced the anti-inflammatory cytokine, TGF-?. In contrast, in UT-CHI, we observed a remarkable expansion of ?? T cells, where the V?2⁺ ?? T cells comprised of an elevated proportion of terminally differentiated cells producing high levels of IFN-? but very low levels of TGF-?. We also found that this loss of regulatory feature of ?? T cells in CHI was a lasting impairment as we did not find recovery of TGF-? production even in ART-CHI patients successfully treated for more than 5?years. Our data therefore suggest that during the primary HIV infection, V?2⁺ ?? T cells may act as Tregs controlling immune activation through production of TGF-?. However, in CHI, ?? T cells transform from an anti-inflammatory into pro-inflammatory cytokine profile and participate in sustenance of immune activation.

SUBMITTER: Bhatnagar N

PROVIDER: S-EPMC5622291 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Potential Role of Vδ2<sup>+</sup> γδ T Cells in Regulation of Immune Activation in Primary HIV Infection.

Bhatnagar Nupur N Girard Pierre-Marie PM Lopez-Gonzalez Moises M Didier Céline C Collias Lio L Jung Corinne C Bollens Diane D Duvivier Claudine C Von Platen Cassandre C Scott-Algara Daniel D Weiss Laurence L

Frontiers in immunology 20170925

Although conventional regulatory T cells (Tregs) are sufficient in controlling low residual T-cell activation in ART-treated patients, they are not efficient in controlling exaggerated immune activation associated with high levels of HIV replication in primary HIV infection (PHI). Our previous data suggested that double negative (DN) T cells including mainly γδ DN T cells play a role in the control of immune activation in PHI. Since γδ T cells are capable of exerting regulatory functions, we inv ...[more]

PMID: 28993778

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Project description:BackgroundWe previously reported that Vδ2+Vγ9+ γδ T cells were significantly decreased in multiple sclerosis (MS) patients without disease-modifying therapies (untreated MS) and were negatively correlated with Expanded Disability Status Scale (EDSS) scores, suggesting protective roles of Vδ2+Vγ9+ γδ T cells. Interferon-β (IFN-β) is one of the first-line disease-modifying drugs for MS. However, no previous studies have reported changes in γδ T cell subsets under IFN-β treatment. Therefore, we aimed to clarify the effects of the long-term usage of IFN-β on γδ T cell subsets in MS patients.MethodsComprehensive flow cytometric immunophenotyping was performed in 35 untreated MS and 21 MS patients on IFN-β for more than 2 years (IFN-β-treated MS) including eight super-responders fulfilling no evidence of disease activity criteria, and 44 healthy controls (HCs).ResultsThe percentages of Vδ2+Vγ9+ cells in γδ T cells were significantly lower in untreated and IFN-β-treated MS patients than in HCs. By contrast, the percentages of Vδ1-Vδ2-Vγ9- cells in γδ T cells were markedly higher in IFN-β-treated MS patients than in HCs and untreated MS patients (both p < 0.001). A significant negative correlation between the percentages of Vδ2+Vγ9+ cells in γδ T cells and EDSS scores was confirmed in untreated MS but not evident in IFN-β-treated MS. Moreover, class-switched memory B cells were decreased in IFN-β-treated MS compared with HCs (p < 0.001) and untreated MS patients (p = 0.006). Interestingly, the percentages of Vδ1-Vδ2-Vγ9- cells in γδ T cells were negatively correlated with class-switched memory B cell percentages in all MS patients (r = - 0.369, p = 0.005), and the percentages of Vδ1-Vδ2-Vγ9- cells in Vδ1-Vδ2- γδ T cells were negatively correlated with EDSS scores only in IFN-β super-responders (r = - 0.976, p < 0.001).ConclusionsThe present study suggests that long-term usage of IFN-β increases Vδ1-Vδ2-Vγ9- γδ T cells, which are associated with a better outcome, especially in IFN-β super-responders. Thus, increased Vδ1-Vδ2-Vγ9- cells together with decreased class-switched memory B cells may contribute to the suppression of disease activity in MS patients under IFN-β treatment.

Dataset Information

Potential Role of V?2⁺ ?? T Cells in Regulation of Immune Activation in Primary HIV Infection.

Publications

Potential Role of Vδ2<sup>+</sup> γδ T Cells in Regulation of Immune Activation in Primary HIV Infection.

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Potential Role of V?2+ ?? T Cells in Regulation of Immune Activation in Primary HIV Infection.

Publications

Potential Role of Vδ2<sup>+</sup> γδ T Cells in Regulation of Immune Activation in Primary HIV Infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Potential Role of V?2⁺ ?? T Cells in Regulation of Immune Activation in Primary HIV Infection.