New research has identified that a key protein called PEA-15 stops T-cell proliferation by blocking the cell's ability to reproduce. The control of T-cell proliferation is essential in preventing certain blood cancers and autoimmune diseases, as well as the orchestration of the immune response to infection. Findings of the study are reported in a recent online issue of The FASEB Journal, a publication of The Federation of American Societies for Experimental Biology.
A team of researchers from the University of Hawai'i Cancer Research Center, Rutgers University and Washington University in St. Louis examined the normal function of PEA-15, which acts as a tumor suppressor in some cancers including brain, ovarian and breast cancers. They found that PEA-15 normally controls lymphocyte (white blood cell) proliferation.
To determine the normal role of this protein, investigators examined mice lacking PEA-15. They found that those without the protein had both spatial learning disabilities and a pronounced increase in lymphocyte (white blood cell) proliferation. Upon closer inspection, they further found that loss of PEA-15 particularly affected a group of lymphocytes called T-cells. T-cells are involved in killing invading pathogens as well as stimulating more long-term immunity. The PEA-15 protein works by acting as a brake on a group of proteins that activate cell cycling and proliferation when they recognize a signal from an invading organism. Lymphocytes without PEA-15 continue proliferating beyond normal response levels as if they lack the "brakes" to stop.
"Understanding how T-cell expansion is controlled at the molecular level should lead to new methods to control the immune response during infection as well as perhaps helping the development of novel ways to utilize these cells to attack tumors," said Joe Ramos, Ph.D. principal investigator and assistant professor in natural products and cancer biology at the University of Hawaii. "Dysregulation of PEA-15 function might also play a role in the development or progression of lymphomas or leukemias," he added. "Finding ways to regain normal function of PEA-15 might contribute to identification of new approaches to treat these cancers. "
The study, titled "The death effector domain protein PEA-15 negatively regulates T-cell receptor signaling" was funded by grants from the National Institutes of Health (NCI) to Joe W. Ramos at the University of Hawai'i Cancer Research Center and Andrey Shaw from Washington University in St. Louis. Support for Guy Werlen at Rutgers University came from the New Jersey Commission on Cancer Research.