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Regulatory T cells harbor HIV/SIV virus during antiviral drug treatment

Murph

:)
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1,792
https://medicalxpress.com/news/2017-10-regulatory-cells-harbor-hivsiv-virus.html

Scientists at Yerkes National Primate Research Center, Emory University have identified an additional part of the HIV reservoir, immune cells that survive and harbor the virus despite long-term treatment with antiviral drugs.


Their findings are scheduled for publication in Immunity.

The cells display a molecule called CTLA4, the target of an FDA-approved cancer immunotherapy drug, ipilimumab. This information should help those trying to eradicate HIV from the body.

Researchers led by Mirko Paiardini, PhD, infected macaques with HIV's relative SIV and treated them with standard antiviral drugs similar to what humans receive for HIV. At the time of analysis, almost all the animals (8 out of 9) showed undetectable SIV in their blood. The team probed for CD4+ memory T cells, which are known to shelter persistent virus.

"We found that a certain group of memory CD4+ T cells displaying CTLA4, but not another co-inhibitor receptor called PD1, harbor viral DNA at higher frequencies than other groups of memory CD4+ T cells," says Paiardini, associate professor of pathology and laboratory medicine. "These cells can be found in multiple tissues, such as lymph node, spleen, gut and bone marrow, and contain replication-competent and infectious virus."

The Yerkes team worked with researchers at NCI/Leidos Frederick led by Jacob Estes, PhD, using a technique called "DNAscope", to visualize latently infected cells in lymph nodes. Previous research had shown that HIV-infected cells persist in regions of the lymph nodes called B cell follicles. The newly identified group of infected cells is found outside the B cell follicles.

Working in close collaboration with Rafick Sekaly, PhD, at Case Western Reserve University, the research team also showed that the CTLA4-positive PD1-negative cells have the characteristics of regulatory T cells, whose job is to put a brake on the immune system and prevent it from getting too excited.

"It provides a strong rationale for targeting these cells," Paiardini says. "Depleting latently infected T-regs can not only reduce the reservoir, but also induce a stronger antiviral immune response."

The researchers also worked with Vincent Marconi, MD, a physician treating HIV in Atlanta, to confirm that similar cells were present in human lymph nodes. The human samples came from six HIV-positive individuals who had been on antiviral drugs for an average of three years.

Based on the team's findings, CTLA-4 should be considered as an additional target when designing immunotherapies aimed at purging the viral reservoir, Paiardini says.


More information: Immunity (2017). DOI: 10.1016/j.immuni.2017.09.018
 

Murph

:)
Messages
1,792
To me, this sort of thing tells us to keep an open mind. If viruses can be 'hiding' in HIV, one of the most rigorously studied diseases there is, they can probably still be implicated in me/cfs despite the absence of evidence so far.

I still consider an autoimmune etiology the most probable but I don't think the door is fully closed on the alternatives.
 
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Simon

Senior Member
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Monmouth, UK
To me, this sort of thing tells us to keep an open mind. If viruses can be 'hiding' in HIV, one of the most rigorously studied diseases there is, they can probably still be implicated in me/cfs despite the absence of evidence so far.

I still consider an autoimmune etiology the most probable but I don't think the door is fully closed on the alternatives.
I’m not sure. This work is really looking at why HIV is hard to completely eradicate from the body when it’s still cleared from the blood (which still usually constitutes effective treatment). That’s different from trying to understand what’s causing day to day Mecfs. Thanks for posting this interesting work, though.
 

halcyon

Senior Member
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2,482
That’s different from trying to understand what’s causing day to day Mecfs.
Nobody has proved that persistent viral infection isn't the cause of day to day ME/CFS.

I'll call it now, I think things like what you're seeing here will become important in upcoming ME research. You are going to hear about PD-1, CTLA-4, and I bet many other T cell counter-regulatory exhaustion signals (TIM-3, LAG-3, etc.). Keep an eye on Mark Davis and also the Cornell team.