CD4+ CD52lo T-cell expression contributes to the development of systemic lupus erythematosus

Masataka Umeda; Tomohiro Koga; Kunihiro Ichinose; Takashi Igawa; Tomohito Sato; Ayuko Takatani; Toshimasa Shimizu; Shoichi Fukui; Ayako Nishino; Yoshiro Horai; Yasuko Hirai; Shin-Ya Kawashiri; Naoki Iwamoto; Toshiyuki Aramaki; Mami Tamai; Hideki Nakamura; Kazuo Yamamoto; Norio Abiru; Tomoki Origuchi; Yukitaka Ueki; Atsushi Kawakami

doi:10.1016/j.clim.2017.10.004

CD4⁺ CD52^lo T-cell expression contributes to the development of systemic lupus erythematosus

Clin Immunol. 2018 Feb:187:50-57. doi: 10.1016/j.clim.2017.10.004. Epub 2017 Oct 13.

Authors

Masataka Umeda¹, Tomohiro Koga², Kunihiro Ichinose³, Takashi Igawa¹, Tomohito Sato¹, Ayuko Takatani¹, Toshimasa Shimizu¹, Shoichi Fukui¹, Ayako Nishino¹, Yoshiro Horai⁴, Yasuko Hirai¹, Shin-Ya Kawashiri¹, Naoki Iwamoto¹, Toshiyuki Aramaki⁵, Mami Tamai¹, Hideki Nakamura¹, Kazuo Yamamoto⁶, Norio Abiru⁷, Tomoki Origuchi⁸, Yukitaka Ueki⁵, Atsushi Kawakami¹

Affiliations

¹ Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
² Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address: [email protected].
³ Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address: [email protected].
⁴ Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Department of Rheumatology, Clinical Research Center, National Hospital Organization Nagasaki Medical Center.
⁵ Department of Rheumatology, Sasebo Chuo Hospital, Nagasaki, Japan.
⁶ Biomedical Research Support Center, Nagasaki University School of Medicine, Nagasaki, Japan.
⁷ Department of Endocrinology and Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
⁸ Department of Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

PMID: 29031579
DOI: 10.1016/j.clim.2017.10.004

Abstract

The cell-surface glycoprotein CD52 is widely expressed in lymphocytes. CD4⁺CD52^hi T cells are functioning suppressor CD4⁺T cells. We investigated the role of the immune regulation of CD4⁺CD52 T cells in systemic lupus erythematosus (SLE). CD4⁺CD52^lo T cells were increased in SLE patients, in positive correlation with SLEDAI, anti-ds-DNA antibody, and IgG concentration. Circulating follicular helper-like T cells (Tfh-like cells) were also increased in SLE, in positive correlation with CD4⁺CD52^lo T cells. Chemokine receptor 8 (CCR8) expression in CD4⁺CD52^lo T cells was increased. In vitro experiments using CD4 T cells of SLE patients showed that thymus and activation-regulated chemokine (TARC), a ligand of CCR8, contributed to the development of CD4⁺CD52^hi T cells into CD4⁺CD52^lo T cells. Our findings suggest that CD4+CD52lo T-cell upregulation is involved in the production of pathogens by autoantibodies, and TARC may contribute to the development of SLE through an aberrant induction of CD4⁺CD52^lo T cells.

Keywords: CD52; Systemic lupus erythematosus; T cells.

Publication types

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

MeSH terms

Adolescent
Adult
Antibodies, Antinuclear / immunology
Autoantibodies / immunology
CD4-Positive T-Lymphocytes / immunology*
CD52 Antigen / immunology*
Case-Control Studies
Chemokine CCL17 / immunology*
Female
Humans
Immunoglobulin G / immunology
In Vitro Techniques
Lupus Erythematosus, Systemic / immunology*
Male
Middle Aged
Receptors, CCR8 / immunology
Severity of Illness Index
Up-Regulation
Young Adult

Substances

Antibodies, Antinuclear
Autoantibodies
CCL17 protein, human
CCR8 protein, human
CD52 Antigen
CD52 protein, human
Chemokine CCL17
Immunoglobulin G
Receptors, CCR8