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International Immunology Advance Access originally published online on February 20, 2007
International Immunology 2007 19(4):477-486; doi:10.1093/intimm/dxm012
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Nooruddin Khan1, Sheikh Ghousunnissa1, SenthilKumar M. Jegadeeswaran1, Dorairajan Thiagarajan2, Seyed E. Hasnain1,3,4 and Sangita Mukhopadhyay1

1 Laboratory of Molecular Cell Biology Center for DNA Fingerprinting and Diagnostics, Hyderabad, India
2 Indian Immunologicals Ltd, Hyderabad, India
3 Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India
4 University of Hyderabad, Hyderabad, India

Correspondence to: S. Mukhopadhyay; E-mail: sangita{at}cdfd.org.in

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-{alpha}) 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-{alpha} and other effector responses such as bacterial cytotoxicity and production of ROS. Nuclear factor-kappaB (NF-{kappa}B) was found to be increased with anti-B7-1/B7-2 mAb treatment. Inhibition of NF-{kappa}B activity by over-expression of phosphorylation-defective I-kappaB alpha in anti-B7-1/B7-2 mAb-treated macrophages decreased TNF-{alpha} production. These data indicate that anti-B7-1 and anti-B7-2 mAbs can trigger innate-effector responses in macrophages by activating NF-{kappa}B-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.

Keywords: anti-B7-1/B7-2 mAb, autoimmunity, macrophage, NF-kappaB, TNF-alpha


Transmitting editor: M. Feldmann

Received 25 May 2006, accepted 23 January 2007.


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