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

Eur J Immunol. 2025 Jan;55(1):e202451279. doi: 10.1002/eji.202451279.

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.

Keywords: HAM; HTLV‐1; Sjögren's syndrome; Treg; anti‐Ro/SS‐A antibody.

MeSH terms

  • Aged
  • Autoantibodies / immunology
  • B-Lymphocytes* / immunology
  • Cell Differentiation / immunology
  • Cell Line
  • Coculture Techniques
  • Female
  • HTLV-I Infections / complications
  • HTLV-I Infections / immunology
  • Human T-lymphotropic virus 1* / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Intercellular Adhesion Molecule-1 / immunology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Male
  • Middle Aged
  • Sjogren's Syndrome* / immunology
  • T-Lymphocytes / immunology

Substances

  • Immunoglobulin G
  • Autoantibodies
  • Intercellular Adhesion Molecule-1