Regulatory T and B lymphocytes in a spontaneous autoimmune polyneuropathy

Summary B7‐2 –/– non‐obese diabetic (NOD) mice develop a spontaneous autoimmune polyneuropathy (SAP) that mimics the progressive form of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this study, we focused on the role of regulatory T cells (T regs ) and regulatory B cells (B regs ) in SAP. We found that deletion of B7‐2 in female NOD mice led to a lower frequency and number of T regs and B regs in spleens and lymph nodes. T regs but not B regs suppressed antigen‐stimulated splenocyte proliferation, whereas B regs inhibited the T helper type 1 (Th1) cytokine response. Both T regs and B regs induced an increase in CD4 + interleukin (IL)−10 + cells, although less effectively in the absence of B7‐2. Adoptive transfer studies revealed that T regs , but not B regs , suppressed SAP, while B regs attenuated disease severity when given prior to symptom onset. B cell deficiency in B cell‐deficient (muMT)/B7‐2 –/– NOD mice prevented the development of SAP, which would indicate that the pathogenic role of B cells predominates over its regulatory role in this model. We conclude that B regs and T regs control the immunopathogenesis and progression of SAP in a non‐redundant fashion, and that therapies aimed at expansion of B regs and T regs may be an effective approach in autoimmune neuropathies.