Protein identified that turns off HIV-fighting T cells

November 10, 2008

In HIV-infected patients the body's immune system is unable to fight off the virus. A new study to be published online on November 10th in the Journal of Experimental Medicine shows that T cells in HIV-infected individuals express a protein called TIM-3, which inactivates their virus killing capacity. Blocking this protein, the study suggests, might one day help patients to eliminate HIV as well as other chronic infections.

Large numbers of virus-fighting T cells can be found in the blood of most chronically infected HIV patients. However these cells eventually become exhausted and cannot function. To identify the cause of this exhaustion, a team of researchers at the University of Toronto, lead by Mario Ostrowski, compared blood from healthy individuals and HIV patients. In the patients, TIM-3 was found on a large number of HIV-specific T cells, and the number of TIM-3-positive cells increased with the severity of infection.

Under normal circumstances, exposing T cells to bits of virus causes the cells to replicate and produce virus-killing chemicals. Cells expressing TIM-3, however, were unreactive and TIM-3 was to blame; disrupting its signals restored the cells' virus-fighting functions. TIM-3 normally gets expressed on T cells after they carry out their normal function, perhaps as a way to turn the cells off and thus prevent excessive inflammation. But during HIV infection, persistent TIM-3 expression may help the virus avoid T cell attack.

Whether HIV infection itself induces or sustains TIM-3 is not known. Still, blocking the protein might be a useful way to control virus that persists despite antiretroviral therapy.

Rockefeller University Press

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