Anti-B7-1/B7-2 antibody elicits innate-effector responses in macrophages through NF- B-dependent pathway

• Published in: International immunology 2007-04, Vol.19 (4), p.477-486
• Main Authors: Khan, N., Ghousunnissa, S., Jegadeeswaran, S. M., Thiagarajan, D., Hasnain, S. E., Mukhopadhyay, S.
• Format: Article
• Language: English
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxm012

Blocking T cell co-stimulatory signals by anti-B7-1/B7-2 mAb is an attractive approach to treat autoimmune diseases. However, anti-B7-1/B7-2 mAb treatment is known to exacerbate autoimmune diseases through mechanisms not fully understood. Tumor necrosis factor alpha (TNF-α) and reactive oxygen species (ROS) also play important roles in determining the clinical outcome of autoimmune diseases. In this study, we demonstrate that the anti-B7-1 and the anti-B7-2 mAbs activate macrophages for higher induction of TNF-α and other effector responses such as bacterial cytotoxicity and production of ROS. Nuclear factor-kappaB (NF-κB) was found to be increased with anti-B7-1/B7-2 mAb treatment. Inhibition of NF-κB activity by over-expression of phosphorylation-defective I-kappaB alpha in anti-B7-1/B7-2 mAb-treated macrophages decreased TNF-α production. These data indicate that anti-B7-1 and anti-B7-2 mAbs can trigger innate-effector responses in macrophages by activating NF-κB-signaling pathway. Our results suggest that the B7 molecules are not only essential for induction of adaptive immune responses but also play roles in activation of innate immune responses.