For much of the time our T cellsthe white blood cells that act as the police of the immune systemare in what immunologists call a "quiescent state," a sort of standby mode. For years, scientists have wondered if quiescence occurred by default or whether T cells need to work at remaining silent. Now, researchers at The Wistar Institute provide the first direct proof that a protein, called Foxp1, actively maintains this state of quiescence in T cells until the cells are called upon by other parts of the immune system.
Their findings, which appear online through Nature Immunology ahead of print publication, could one day enable researchers to activate T cells to fight diseases such as cancer, which can go undetected or unrecognized by the immune system. In fact, the researchers report that knocking out the Foxp1 protein in mice activates T cells, allowing the cells to work in their policing function.
"T cell quiescence has been a big mystery in immunology with some obvious and profound implications for treating illness by manipulating the immune system," said Hui Hu, Ph.D., senior author of the study and assistant professor in the Immunology Program at The Wistar Institute. "We believe we have provided evidence that quiescence is not just a passive, default state, and we are now beginning to understand the molecular mechanisms by which it happens."
Mature T cells are generated in the thymus, an organ located in front of heart, and then exit into the periphery. There, these T cells are in a "nave," quiescent state, awaiting orders to act. Activation primarily requires antigen-presenting cell, which offers up an antigen (a particle that the immune system recognizes as "foreign") to the T cell Receptor (TCR). This activated TCR, then, gives the T cell specificity.
Foxp1 is a transcription factor, a protein that binds to DNA and causes the cell to reador transcribespecific genes. The Hu laboratory had previously shown tha
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The Wistar Institute