An important factor controlling the process in which T immune cell responses become progressively weaker during chronic viral infections is reported in a study published online in Nature Immunology this week. Manipulating the activity of this factor may be beneficial in certain chronic infections, such as HIV, and cancers.
Ananda Goldrath and colleagues looked at mouse T cells with elevated amounts of HIF-1-a transcription factor with a well-established role in the response to cellular hypoxia (lack of adequate oxygen supply). They found that the T cells produced greatly enhanced responses to viral infection and failed to become exhausted during a normally chronic infection. T cells in these high HIF-1 expressors were also far more efficient at controlling experimentally induced cancer. These enhanced responses, however, come at a cost since these mice are also vulnerable to uncontrolled inflammation.