Scientists Discover Possibility Of Revitalizing Immune Cells Of HIV Patients

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Main Category: HIV / AIDS
Also Included In: Immune System / Vaccines;  Infectious Diseases / Bacteria / Viruses
Article Date: 11 Nov 2008 - 8:00 PDT

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Scientists in Canada and the US have discovered a method that apparently restores vitality to certain immune system cells that have become "exhausted" from fighting HIV, thus potentially restoring the ability of the infected person's own immune system to wage war against the virus.

The study was led by Dr Mario Ostrowski, who is based at the Faculty of Medicine at the University of Toronto in Canada , and Dr Douglas Nixon, from the Division of Experimental Medicine at the University of California, San Francisco, USA, and is published in the 10th November issue of the Journal of Experimental Medicine.

One of the reasons the human immunodeficiency virus (HIV) gradually overcomes the body's attempt to resist infection is because the immune system's killer T cells stop attacking the virus. Another study recently identified that a protein, PD-1, sends signals to stop over-inflammation, and this was linked to chronic HIV.

In this study, lead author Brad Jones, from the Department of Immunology at the University of Toronto and colleagues, found that another protein, TIM-3, appears to behave in a similar way.

Studies on autoimmune diseases like multiple sclerosis have already shown that disrupting TIM-3 signals leads to over-inflammation, which is why Jones and colleagues decided to investigate it in relation to HIV.

TIM-3 is a glycoprotein expressed by killer T cells. When expressed, TIM-3 suppresses the production of more killer cells and cytokines, the signalling proteins that help to alert and recruit other immune system cells in the fight against infection and pathogens.

For the study, Jones and colleagues examined and manipulated T cells taken from patients with HIV. They found that:

• High levels of TIM-3 were linked to heavier viral loads (higher level of HIV infection).


• When two types of T cell that are important for resisting HIV, known as CD4+ and CD8+, also expressed TIM-3, they secreted less interferon (IFN)-y and TNF (two cytokines involved in sending signals to recruit more immune cells), than cells without TIM-3.


• Blocking TIM-3 (essentially stopping it from sending signals) reversed this effect (ie cytokine secretion was restored).


• Although blocking TIM-3 and PD-1 leads to similar effects on cytokine production, these molecules were found in different groups of CD8+ T cells.


• TIM-3 expression stayed high, even after the viral loads went down, in half of the participants being treated with antiretrovirals (a class of drugs used to treat retroviruses like HIV).

The researchers suggested one explanation for the last result could be that once TIM-3 expression is switched on, it can't be reversed in some people, and that disrupting its signal might be a way to control HIV that resists treatment.

They concluded that:

"Thus, Tim-3 represents a novel target for the therapeutic reversal of HIV-1-associated T cell dysfunction."

HIV isn't the only virus that "exhausts" T cells, and the mechanisms through which viruses and TIM-3 interact are still a mystery. But perhaps restoring vitality to exhausted T cells can also be a way to fight other viral infections.

"Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection."
R. Brad Jones, Lishomwa C. Ndhlovu, Jason D. Barbour, Prameet M. Sheth, Aashish R. Jha, Brian R. Long, Jessica C. Wong, Malathy Satkunarajah, Marc Schweneker, Joan M. Chapman, Gabor Gyenes, Bahareh Vali, Martin D. Hyrcza, Feng Yun Yue, Colin Kovacs, Aref Sassi, Mona Loutfy, Roberta Halpenny, Desmond Persad, Gerald Spotts, Frederick M. Hecht, Tae-Wook Chun, Joseph M. McCune, Rupert Kaul, James M. Rini, Douglas F. Nixon, and Mario A. Ostrowski.
Journal of Experimental Medicine published online November 10, 2008.
DOI: 10.1084/jem.20081398

Click here for Abstract.

Sources: Journal of Experimental Medicine.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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