Dataset Information

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

ABSTRACT:

Background

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 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.

Methods

Comprehensive 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).

Results

The 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).

Conclusions

The 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.

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.