Rejuvenating the Immune System to Fight HIV

Author:  Tetyana Pekar
Institution:  University of Toronto
Date:  December 2008

Human Immunodeficiency Virus, HIV, causes AIDS by attacking the immune system and by impairing the body's ability to fight infection. There is no cure for AIDS, which afflicts approximately 33 million people worldwide presently.

The current treatment for HIV infection, antiretroviral medication, functions by slowing its progression to AIDS. However, it is too expensive for the majority of those infected with HIV and becomes ineffective after years of use. Thus, there is a great urgency to develop better and cheaper treatments.

Recently, an exciting new study, led by Dr Mario Ostrowski at the University of Toronto and Dr. Douglas Nixon at the University of California, San Francisco, discovered that blocking a molecule which is upregulated in non-functioning immune cells rejuvenated the cell's ability to fight against HIV. This research, published in the November 24th issue of Journal of Experimental Medicine, offers a novel treatment target for HIV drugs.

HIV infection progresses to AIDS because the immune cells that initially fight the infection become less functional and lose their ability to fight the virus. "Previous studies have shown that Tim-3 is expressed on Th1 cells, and is often upregulated to suppress immune responses that have already 'done' their job," said Dr. Lishomwa Ndhlovu, a co-author in the study. Th1 cells are the body's first line of defense against infections.

Normally Tim-3 functions as a negative regulator, by shutting down the activated immune cells in order to prevent too much inflammation.

The scientists found that Tim-3 expression strongly correlated with HIV progression. They then created a molecule that blocked the Tim-3 signal, which they predicted would result in an improvement. Excitingly, their predictions proved to be correct, as blocking the pathway in vitro rescued the cell's ability to fight the infection.

"The next step is to attempt Tim-3 blockade in animal models," said Dr. Ostrowski. The hope is that the pathway "could be manipulated to revive exhausted and dysfunctional T cell responses (Th1 cell) in HIV infected persons and improve the ability of T cells to suppress virus," added Dr. Ndhlovu.

One strategy proposed by the researchers would be to prevent Tim-3 signaling by creating a soluble Tim-3 protein that would "mop up" molecules that bind and activate Tim-3. Alternatively, developing reagents that would reverse the Tim-3 pathway may minimize any unwanted effects arising from the prevention of Tim-3 signaling altogether.

Written by: Tetyana Pekar

Edited by: Brandy Sullivan and Matthew Getz

Published by: Hoi See Tsao