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

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⁺CD127^low 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.