Enzyme Expression Regulates Immune Response

Researchers working with a mouse model have found that expression of the enzyme indoleamine 2,3 dioxygenase (IDO) on the surface of immune dendritic cells determines whether they activate or suppress T-cell response.

Capitalizing on recent findings that the drug CTLA4-Ig, a reagent designed to block the action of T-cells, induced IDO in dendritic cells, investigators at the Medical College of Georgia (Augusta, USA) treated normal and IDO knock-out mice with the drug. They found that CTLA4-Ig did not induce IDO expression in macrophages or lymphoid cells. On the other hand, induction of IDO completely blocked clonal expansion of T-cells from transgenic mice following adoptive transfer, whereas CTLA4-Ig treatment did not block T-cell clonal expansion in IDO-deficient recipients. These findings were published in the August 15, 2003, issue of the Journal of Immunology.

"One of the things we argue in this paper is that we can use IDO to help us find out if dendritic cells are going to stimulate the immune system or turn it off. If they express IDO, they will not stimulate T-cells to respond. If they do not express IDO, they are likely to stimulate immune responses once they mature,” explained senior author Dr. Andrew L. Mellor, director of the Immunotherapy Center at the Medical College of Georgia. "It comes back to the unifying theme of what it is at the molecular and cellular level that regulates whether the immune system is going to respond or not to any given circumstance.”



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