Double-negative T cells are absolutely elevated in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis

Yan Qin; Yanlin Wang; Yanyao Wu; Min Feng; Xiangcong Zhao; Chong Gao; Hui Guo; Jing Luo

doi:10.1016/j.molimm.2021.01.014

Double-negative T cells are absolutely elevated in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis

Mol Immunol. 2021 Apr:132:250-259. doi: 10.1016/j.molimm.2021.01.014. Epub 2021 Jan 29.

Authors

Yan Qin¹, Yanlin Wang², Yanyao Wu¹, Min Feng², Xiangcong Zhao², Chong Gao³, Hui Guo⁴, Jing Luo⁵

Affiliations

¹ The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
² Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
³ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Division of Nephrology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, China; Division of Nephrology, Department of Medicine, Shenzhen Baoan Shiyan People's Hospital, Shenzhen, Guangdong, 518005, China. Electronic address: ghty966@126.com.
⁵ Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, China. Electronic address: ljty966@hotmail.com.

PMID: 33518366
DOI: 10.1016/j.molimm.2021.01.014

Abstract

CD3⁺CD4^-CD8^- [double-negative (DN)] T cells play vital roles in the pathogenesis of autoimmune disorders. In this study, we investigated the exact level of DN T cells in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Forty patients with active AAV and 19 healthy controls (HCs) were enrolled in this study. Peripheral mononuclear cells were characterised phenotypically via flow cytometry. The potential clinical value of DN T cells was then assessed by the receiver operating characteristic (ROC) curves. The percentage (p < 0.001) and absolute number (p = 0.028) of DN T cells were found to be significantly higher in patients with AAV than in HCs. Relative to HCs, a lower percentage of DN T cells from patients with AAV was of the CD62L⁺CD45RO⁺ phenotype (p = 0.024), a higher percentage of these cells was of the CD62L-CD45RO- phenotype (p = 0.043). Patients with AAV had increased percentages of DN T cells expressing interferon (IFN)-γ (p = 0.032), interleukin (IL)-4 (p = 0.039) and IL-17 (p = 0.042). Furthermore, the percentages of IL-17-producing CD4⁺ T cells and IFN-γ-producing CD8⁺ T cells were significantly higher in patients with AAV than in HCs (p = 0.014, p = 0.008). Compared with the CD4⁺ and CD8⁺ T-cell subsets, DN T cells had the highest fractions of intracellular IL-17 in HCs and patients with AAV (both p < 0.001). In patients with AAV and renal damage, the percentage of DN T cells was expanded relative to that in patients without renal damage (p = 0.016). In addition, conventional methylprednisolone effectively reduced the percentage and overall number of DN T cells in patients with AAV (p = 0.028, p = 0.007). DN T cells represent a T-lymphocyte subset that produces inflammatory cytokines (IFN-γ, IL-4 and IL-17) and is absolutely elevated in patients with AAV. Additional investigations are required to determine their precise role in patients with AAV.

Keywords: Antineutrophil cytoplasmic autoantibody–associated vasculitis; Double- negative T cells; Inflammatory cytokine; Renal damage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antibodies, Antineutrophil Cytoplasmic / immunology*
CD4-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / immunology*
Cytokines / immunology
Female
Humans
Male
Middle Aged
Vasculitis / immunology*

Substances

Antibodies, Antineutrophil Cytoplasmic
Cytokines