Low mucosal-associated invariant T-cell number in peripheral blood of patients with immune thrombocytopenia and their response to prednisolone.

Takaaki Maekawa,Yosuke Okada,Yukiko Osawa,Shinichi Kobayashi,Ayako Kobayashi,Masahiro Teramoto,Ken Sato,Toshikatsu Horiuchi,Noriaki Tachi,Fumihiko Kimura,Toshikuni Kawamura,Shoichiro Kato,Johan K Sandberg

doi:10.1371/journal.pone.0207149

Takaaki Maekawa, Yosuke Okada + Show 11 more

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https://doi.org/10.1371/journal.pone.0207149

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Journal: PloS one	Publication Date: Nov 8, 2018
Citations: 5	License type: CC BY 4.0

Affiliation: National Defense Medical College

Abstract

Mucosal-associated invariant T (MAIT) cells help protect against certain infections and are related to some autoimmune diseases. Immune thrombocytopenia (ITP) is a relatively rare hematological autoimmune disease associated with low platelet count. We designed a cross-sectional study wherein we examined peripheral blood samples of patients with ITP for the number of MAIT cells (CD3+TCR-Vα7.2+CD161+IL-18Rα+ lymphocytes) and their CD4/8 subsets (by flow cytometry) and levels of cytokines (by multiplex assays). The study cohort included 18 patients with ITP and 20 healthy controls (HCs). We first compared the number of MAIT cells between HCs and patients with ITP and then performed subgroup analysis in patients with ITP. The number of total MAIT cells in patients with ITP was significantly lower than that in HCs (p < 0.0001), and the CD4−CD8+ subset of MAIT cells showed the same trend. Moreover, patients with ITP refractory to prednisolone exhibited a significantly lower number of total MAIT and CD4−CD8+ MAIT cells than patients sensitive to prednisolone. The number of total MAIT and CD4−CD8+ MAIT cells was not correlated with the response to thrombopoietin receptor agonist treatment or with Helicobacter pylori infection. We found no relation between cytokine levels and response to prednisolone treatment, although the levels of IP-10 and RANTES showed a correlation with the number of total MAIT and CD4−CD8+ MAIT cells. In conclusion, total MAIT and CD4−CD8+ MAIT cells in peripheral blood were decreased in patients with ITP, correlating with their response to prednisolone.

Highlights

Mucosal-associated invariant T (MAIT) cells produce various cytokines and control various types of immunoreactions
We found that the number and frequency of total MAIT cells within blood CD3+ T cells in immune thrombocytopenia (ITP) patients were significantly lower than those in healthy controls (HCs) (p < 0.0001 and p = 0.0123, respectively) (Fig 1A)
Quantitative and functional deficiencies of MAIT cells in peripheral blood (PB) have been reported in infections and autoimmune diseases, including human HIV infection, tuberculosis, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, and autoimmune liver disease [4, 9, 10,11,12,13,14,15, 25, 26]

Summary

Introduction

Mucosal-associated invariant T (MAIT) cells produce various cytokines and control various types of immunoreactions. They are innate T lymphocytes that connect innate and acquired immunities. MAIT cells are activated by pro-inflammatory cytokines, such as IL-12 and IL-18, in a T-cell receptor (TCR)-independent manner [5]. MAIT cells secrete pro-inflammatory cytokines, such as IL-17 and IFNγ, and exhibit cytotoxic effects [1, 6]. MAIT cells express the specific invariant T-cell receptor alpha chain (TCR-Vα7.2), CD161 (one of the C-type lectins), and interleukin-18-receptor alpha chain (IL18Rα), which are used as specific surface markers [4, 7]. The majority of MAIT cells are CD4−CD8+, followed by CD4−CD8− [4]

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