Dataset Information

Long-term use of interferon-? in multiple sclerosis increases V?1^-V?2^-V?9^- ?? T cells that are associated with a better outcome.

ABSTRACT:

Background

We previously reported that V?2⁺V?9⁺ ?? 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 V?2⁺V?9⁺ ?? T cells. Interferon-? (IFN-?) is one of the first-line disease-modifying drugs for MS. However, no previous studies have reported changes in ?? T cell subsets under IFN-? treatment. Therefore, we aimed to clarify the effects of the long-term usage of IFN-? on ?? T cell subsets in MS patients.

Methods

Comprehensive flow cytometric immunophenotyping was performed in 35 untreated MS and 21 MS patients on IFN-? for more than 2 years (IFN-?-treated MS) including eight super-responders fulfilling no evidence of disease activity criteria, and 44 healthy controls (HCs).

Results

The percentages of V?2⁺V?9⁺ cells in ?? T cells were significantly lower in untreated and IFN-?-treated MS patients than in HCs. By contrast, the percentages of V?1^-V?2^-V?9^- cells in ?? T cells were markedly higher in IFN-?-treated MS patients than in HCs and untreated MS patients (both p < 0.001). A significant negative correlation between the percentages of V?2⁺V?9⁺ cells in ?? T cells and EDSS scores was confirmed in untreated MS but not evident in IFN-?-treated MS. Moreover, class-switched memory B cells were decreased in IFN-?-treated MS compared with HCs (p < 0.001) and untreated MS patients (p = 0.006). Interestingly, the percentages of V?1^-V?2^-V?9^- cells in ?? 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 V?1^-V?2^-V?9^- cells in V?1^-V?2^- ?? T cells were negatively correlated with EDSS scores only in IFN-? super-responders (r = -?0.976, p < 0.001).

Conclusions

The present study suggests that long-term usage of IFN-? increases V?1^-V?2^-V?9^- ?? T cells, which are associated with a better outcome, especially in IFN-? super-responders. Thus, increased V?1^-V?2^-V?9^- cells together with decreased class-switched memory B cells may contribute to the suppression of disease activity in MS patients under IFN-? treatment.

SUBMITTER: Maimaitijiang G

PROVIDER: S-EPMC6743159 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Long-term use of interferon-β in multiple sclerosis increases Vδ1-Vδ2-Vγ9- γδ T cells that are associated with a better outcome.

Maimaitijiang Guzailiayi G Watanabe Mitsuru M Shinoda Koji K Isobe Noriko N Nakamura Yuri Y Masaki Katsuhisa K Matsushita Takuya T Yoshikai Yasunobu Y Kira Jun-Ichi JI

Journal of neuroinflammation 20190913 1

<h4>Background</h4>We 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 ...[more]

PMID: 31519178

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Project description:We recently reported that deletion-type copy number variations of the T cell receptor (TCR) γ, α, and δ genes greatly enhanced susceptibility to multiple sclerosis (MS). However, the effect of abnormal TCR γδ gene rearrangement on MS pathogenesis remains unknown. In the present study, we aimed to clarify γδ TCR repertoire alterations and their relationship to clinical and immunological parameters in MS patients by comprehensive flow cytometric immunophenotyping. Peripheral blood mononuclear cells obtained from 30 untreated MS patients in remission and 23 age- and sex-matched healthy controls (HCs) were stained for surface markers and intracellular cytokines after stimulation with phorbol 12-myristate 13-acetate and ionomycin, and analyzed by flow cytometry. MS patients showed significantly decreased percentages of Vδ2+ and Vδ2+Vγ9+ cells in γδ T cells (pcorr = 0.0297 and pcorr = 0.0288, respectively) and elevated Vδ1/Vδ2 ratios compared with HCs (p = 0.0033). The percentages of interferon (IFN)-γ+Vδ2+ and interleukin (IL)-17A+IFN-γ+Vδ2+ cells in γδ T cells, as well as IFN-γ+ cells in Vδ2+ γδ T cells, were significantly lower in MS patients than in HCs (pcorr < 0.0009, pcorr = 0.0135, and pcorr = 0.0054, respectively). The percentages of Vδ2+ and Vδ2+Vγ9+ cells in γδ T cells were negatively correlated with both the Expanded Disability Status Scale score (r = -0.5006, p = 0.0048; and r = -0.5040, p = 0.0045, respectively) and Multiple Sclerosis Severity Score (r = -0.4682, p = 0.0091; and r = -0.4706, p = 0.0087, respectively), but not with age at disease onset, disease duration, or annualized relapse rate. In HCs, the percentages of Vδ2+ and Vδ2+Vγ9+ cells of total CD3+ T cells had strong positive correlations with the percentage of CD25+CD127low/- cells in CD4+ T cells (r = 0.7826, p < 0.0001; and r = 0.7848, p < 0.0001, respectively), whereas such correlations were totally absent in MS patients. These findings suggest that decreased Vδ2+Vγ9+ γδ T cells are associated with disability in MS. Therefore, the Vδ1/Vδ2 ratio might be a candidate biomarker for predicting disease severity in MS.

Project description: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 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 γδ 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 γδ T cells negatively correlated with CD8 T-cell activation in PHI patients. Furthermore, we found that in these patients, the Vδ2 receptor bearing (Vδ2+) γδ T cells were strongly activated, exhibited low terminal differentiation, and produced the anti-inflammatory cytokine, TGF-β. In contrast, in UT-CHI, we observed a remarkable expansion of γδ T cells, where the Vδ2+ γδ T cells comprised of an elevated proportion of terminally differentiated cells producing high levels of IFN-γ but very low levels of TGF-β. We also found that this loss of regulatory feature of γδ T cells in CHI was a lasting impairment as we did not find recovery of TGF-β production even in ART-CHI patients successfully treated for more than 5 years. Our data therefore suggest that during the primary HIV infection, Vδ2+ γδ T cells may act as Tregs controlling immune activation through production of TGF-β. However, in CHI, γδ T cells transform from an anti-inflammatory into pro-inflammatory cytokine profile and participate in sustenance of immune activation.

Dataset Information

Long-term use of interferon-? in multiple sclerosis increases V?1^-V?2^-V?9^- ?? T cells that are associated with a better outcome.

Background

Methods

Results

Conclusions

Publications

Long-term use of interferon-β in multiple sclerosis increases Vδ1<sup>-</sup>Vδ2<sup>-</sup>Vγ9<sup>-</sup> γδ T cells that are associated with a better outcome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Long-term use of interferon-? in multiple sclerosis increases V?1-V?2-V?9- ?? T cells that are associated with a better outcome.

Background

Methods

Results

Conclusions

Publications

Long-term use of interferon-β in multiple sclerosis increases Vδ1<sup>-</sup>Vδ2<sup>-</sup>Vγ9<sup>-</sup> γδ T cells that are associated with a better outcome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Long-term use of interferon-? in multiple sclerosis increases V?1^-V?2^-V?9^- ?? T cells that are associated with a better outcome.