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Author Topic: Molecule linked to HIV immune Cell Exhaustion...  (Read 1822 times)

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Offline J.R.E.

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  • Joined Dec-2003 Living positive, since 1985.
Molecule linked to HIV immune Cell Exhaustion...
« on: December 12, 2008, 10:27:30 PM »


Molecule Linked to HIV Immune Cell "Exhaustion"
By Michael Smith, North American Correspondent, MedPage Today
Published: November 12, 2008
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.  Earn CME/CE credit
for reading medical news
TORONTO, Nov. 12 -- Researchers here think they've taken the first step toward reviving T cells "exhausted" from fighting HIV.

Such worn-out cells are characterized by an expression of a molecule called Tim-3 (for T cell immunoglobulin and mucin domain-containing molecule 3), according to Mario Ostrowski, M.D., of the University of Toronto, and colleagues.

But blocking the activity of Tim-3 restored the cells' ability to proliferate and to produce cytokines in response to HIV antigens, Dr. Ostrowski and colleagues said online in the Journal of Experimental Medicine.

One of the hallmarks of HIV infection is a progressive loss of function in CD8-positive and CD4-positive T cells, which has been called "T cell exhaustion" the researchers noted. Action Points 

Note that this study associated "T cell exhaustion" with a molecule called Tim-3 and found that blocking Tim-3 appeared to restore the immune cell function.
In a series of experiments, they found that Tim-3 expression on T cells was highly correlated with advancing HIV disease and hypothesized that the molecule was playing a role in T cell exhaustion.

"To test this, we produced a molecule capable of blocking the Tim-3 signal and studied the effect that this had on CD8-positive T cell function in vitro," Dr. Ostrowski said.

"We observed that blocking the Tim-3 pathway rescued those cells and restored their ability to fight off infection," he said.

In the long run, Tim-3 might offer a therapeutic target that could improve the immune response to HIV, he said, although more research is needed. He and his colleagues are planning animal studies as a first step.

The combination of a better immune response and modern HIV medications might increase the chance of clearing the infection, Dr. Ostrowski said. "If we could use both anti-viral agents and enhance the immune response, maybe we could get rid of it," he said.

Because the Tim-3 molecule is known to shut down immune responses in diseases such as multiple sclerosis, the researchers looked at peripheral blood mononuclear cells from 31 HIV patients and nine non-infected people using a Tim-3 antibody to see which cells expressed it.

The cohort included HIV patients with progressive disease and so-called "viral controllers (nonprogressors)" whose infection was not progressing.

On average, 28.5% of the CD8 T cells of uninfected volunteers expressed Tim-3, compared with 52.2% of cells in patients with an early or acute infection and 49.4% in patients with a chronic infection. The differences were significant at P=0.0015 and P=0.0003, respectively.

In contrast, 31.6% of the CD8 cells of viral controllers expressed Tim-3 -- not significantly different from the uninfected volunteers.

A similar pattern was seen for CD4-positive T cells, the researchers said, adding that both observations were also seen in another cohort of 60 HIV-positive volunteers.

For both CD8 and CD4 T cells, the frequency of Tim-3 expression significantly correlated positively with HIV viral load and inversely with absolute CD4 T cell counts (at P<0.0001 for both correlations for CD8 cells and at P=0.0087 and P=0.0273, respectively for CD4 cells).

The level of Tim-3 expression was also correlated positively with the expression of CD38, a marker of T cell activation that is associated with poor prognosis, Dr. Ostrowski said.

When the researchers blocked the activity of Tim-3, they found that "exhausted" CD8 T cells regained the ability to proliferate in the presence of an HIV antigen and also were able to produce more of the cytokine interferon-gamma.

The study was supported by the Canadian Institutes for Health Research, the UCSF Gladstone Institute of Virology & Immunology Center for AIDS Research, the UCSF AIDS Biology Program of the AIDS Research Institute, the NIH, the Cancer Research Institute, the Ontario HIV Treatment Network, the University-wide AIDS Research Program, and the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research.
The researchers said they had no conflicting financial interests.


Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 25 mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg






Diagnosed positive in 1985,.. In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started on  HAART on October 24th, 2003.

 As of 9/16/16,  t-cells are at 501,   Viral load remains <40

Current % is at 12%

 65 years young.

Offline freewillie99

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  • Posts: 326
Re: Molecule linked to HIV immune Cell Exhaustion...
« Reply #1 on: December 13, 2008, 03:38:20 PM »
That was a very interesting read.  I'd like to order up a Tim-3 / PD-1 cocktail, please.
Beware Romanians bearing strange gifts


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