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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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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.

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<sup>+</sup>Vγ9<sup>+</sup> 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<sup>+</sup>Vγ9<sup>+</sup> 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]

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