When suffering from chronic infections (pathogens such as hepatitis C, AIDS, and malaria), the human immune system and pathogens confront each other and enter a long deadlock, and no one can gain an advantage. However, after a period of time, the immune cells are depleted, so that the immune system is destroyed, giving the pathogen an advantage. Now, in a new study, researchers from the Perelman School of Medicine at the University of Pennsylvania are revealing how that happened. These findings also suggest that a new treatment may be used to change the balance of power in chronic infections. Under the leadership of Associate Professor of Microbiology Dr. E. John Wherry, the researchers used model mice suffering from chronic viral infections to map the T-cell responses produced when the immune system was in a chronic state of war. They found that two different types of virus-specific CD8 + T cells-one class expresses high-level protein T-bet and the other class expresses high-level protein Eomes-work together to suppress this infection. In particular, they found that there seemed to be a progenitor-mature cell relationship between the two cell populations. Cells expressing T-bet appear to function as progenitor cells (ie, stem cells). These cells can regenerate and maintain virus-specific T cells by dividing. But they also divide into mature, terminally differentiated cells that express Eomes by dividing. These Eomes-expressing cells are more effective against the virus itself, but are unable to replicate themselves. The researchers found that the two cell populations tended to confine themselves to different anatomical areas in animals infected with the virus. They found that T-bet positive cells exist in the blood and spleen, while Eomes positive cells exist in the liver, bone marrow, and gastrointestinal tract. The researchers then eliminated one of the cell populations by deleting the protein T-bet or Eomes, thereby reducing the immune system's ability to fight this infection, which led to a bias in the body's balance to pathogens. More importantly, this study suggests that new treatment strategies can be used to combat or at least better control chronic infections. For example, if people can maintain these progenitor cells longer, or induce these terminal progeny cells to divide, they may be able to change the balance formed when the infection occurs and maintain control of the infection.
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