Blockade of B-cell activating factor with TACI-IgG effectively reduced Th1 and Th17 cells but not memory T cells in experimental allergic encephalomyelitis mice

Abstract

B-cell activating factor (BAFF) is regarded as a new therapeutic target in autoimmune diseases such as systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Along with other researchers, we have demonstrated that BAFF inhibitor atacicept (TACI-IgG) suppresses lupus and experimental allergic encephalomyelitis (EAE) by reducing the mature B-cell number but not memory B cells. It is however unclear whether TACI-Ig affects pathogenic T cells and memory T cells. In the present study, we found that blocking BAFF with TACI-IgG effectively reduces the pathogenic Th1 and Th17 cells in EAE mice. However, TACI-IgG did not reduce memory CD62L + CD44hiCD4 + and CD62L + CD44hiCD8 + T cells in EAE mice. When interleukin (IL)-15 was neutralized, memory CD62L + CD44hi T cells were significantly reduced in TACI-IgG-treated EAE mice. These results suggest that TACI-IgG is effective in effective controlling Th1 and Th17 cells, but it also increases IL-15 to upregulate memory T cells in EAE mice. The study provides hints for the clinical application of the combination of BAFF-and IL-15-specific therapeutic agents.