Powerful T-Cell Inhibitor Identified

Researchers have found that the protein B7-H4, a member of the B7 family of immune system co-stimulators, powerfully inhibits the immune system response of T cells.

Investigators at the Mayo Clinic (Rochester, MN, USA; www.mayo.edu) cloned the B7-H4 molecule, produced a 3-D computer model, and identified the functional area. The molecule was then produced by genetic engineering and tested on T cells, both in cell culture and in live mice.

The research, published in the June 17, 2003, issue of Immunity, revealed that B7-H4 had a profound inhibitory effect on the growth, cytokine secretion, and development of cytotoxicity in T cells. Administration of B7-H4Ig into mice impaired antigen-specific T cell responses, whereas blockade of endogenous B7-H4 by specific monoclonal antibody promoted T cell responses.

Senior author Dr. Leiping Chen, professor of immunology at the Mayo Clinic, explained, "The immune system is a double-edged sword. It can help and it can damage. It has a positive and a negative capacity, and understanding and controlling these are the key issues for manipulation of diseases with new treatments. This molecule is very important for doing that work because it is a very potent negative regulation component of the immune system. In a tumor, you may have excess B7-H4 turning off T cells all the time. In a normal healthy body, the negative regulators like B7-H4 have to be turned on. This new finding about B7-H4 adds excitement to the possibility of therapeutic manipulation of the immune system.”





Related Links:
Mayo Clinic