Protein Identified that Mediates T-Cell Activation

Reseachers have found that an adapter protein known as CARMA1 mediates activation of several transcription factors essential to controlling multiple genes for inflammation, anti-apoptosis (programmed cell death) and T-cell proliferation. These findings were published in the September 2002 issue of Nature Immunology.

Investigators from the University of Buffalo (NY, USA) were studying the mechanism for activation of a group of transcription factors known as the NF-KB family, which is responsible for a wide range of immune system responses, including the production of interleukin-2 (IL-2), which modulates the production of helper T-cells.

To this end they cloned a CARMA1-deficient T-cell line, and found that lack of this protein selectively impaired the activation of NF-KB, which resulted in defective IL-2 production. Restoring CARMA1 to the cell line also restored the signaling system.

Dr. Xin Lin, assistant professor of microbiology and the senior author of the study explained, "We provide genetic evidence to show that this protein is an important link in the signaling pathway of T-cells. If we can understand T-cell receptor actions, we will be able to shut down the pathway or design drugs to act on the pathway.”

"This finding identified CARMA1 as a potential target for drugs that could be designed to enhance the immune system in immune-compromised patients, dampen it to prevent tissue and organ rejection, and control the proliferation of T-cells to treat leukemia,” said Dr. Lin.



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