T cell turnoff
From Scientific American, December 2007:
HIV is devastating because it attacks and destroys the body’s defense system against pathogens, leaving patients fatally exposed. So what would possess scientists to treat HIV-positive patients with drugs that suppress the immune system? Read more.
Labels: HIV, HIV/AIDS, immunology, Scientific American
posted by Bianca Nogrady at 10:27 AM
6 Comments:
It would appear to me that the biggest, if not the only significant, benefit of this approach (if it indeed proves to work) is a vaccine.
A vaccine that works opposite to the standard ones, by teaching the T-cells to *not* attack the virus when they meet it, and instead have the virus be killed with other chemical (injected) means upon detection.
I would be surprised if this idea hasn't occurred to someone already, or is not implicit in the article, but it would seem a pity not to explore this avenue!
Yiannis Tsiounis, Ph.D.
11:08 AM
This form of therapy is not a vaccine, which stimulates or primes the immune system, but rather a treatment that suppresses the immune system.
The problem with HIV is that T-cells don't attack it - the virus has found a way to hijack the T-cell response to enable its own replication and to disable the natural immune response to invasion.
Immunosuppression would in theory slow down viral replication and hopefully preserve some natural immune function. It is unlikely to 'cure' HIV infection but may at least slow down progression of the disease and reduce the need for such intensive anti-retroviral medication.
In terms of vaccines, so far no one has managed to develop a successful vaccine against HIV as it is such an immunologically complex virus and disease that traditional vaccine approaches just don't work.
I hope that answers your question.
11:15 AM
This will have interesting application in developing immune based therapy for management of HIV infection.Immune suppression will significantly tone down cytokine expression that is responsible for 1) immune activation against Lymphoid organs,Thymus and subsequent damage 2)Activation of CD4 causing viral replication and apoptosis of infected cd4 cells.
After this phase of immune suppression to bring about latency in HIV,immune stimulation will bring up necessary CD4 and CD8 cells and inhibit opportunistic infections.
This is going to be the future of HIV management.
Can I get some references of published studies regarding your observations of Sooty Mangabey and low levels of immune activation and adapting to SIV.
Do they have a normal life expectancy and quality of life(activity) like non infected animals
Sunil Bhaskaran Pune India
2:25 AM
Hi Sunil
thanks for your comments. My information on the sooty mangabey and SIV came from the International AIDS Society conference in Sydney last year, so I'm not sure if or where this data has been published.
However you can view the Powerpoint presentation by Dr Jacob Estes, University of Minnesota, from the IAS conference at www.ias2007.org/pag/ppt/TUSY404.ppt .
I'm afraid I don't know whether the QOL of infected sooty mangabeys is the same as uninfected individuals, but the data suggests they do not develop AIDS-like symptoms or opportunistic infections. Whether they manifest any other symptoms of SIV infection I don't know.
I believe there will be more data on the immunosuppression approach presented at the upcoming CROI 2008 conference.
Bianca
12:38 PM
If we accept the premise that we are dealing with an immunosuppressive disease and, as your article in Scientific American points out, we are using an immunosuppressive agent in most cases to "treat" the HIV positive patient, hasn't this process been used since the first agents(AZT) were used to "treat" HIV positive patients? It appears that the mainstream HIV therapy has gone from most toxic to less toxic chemotherapeutic drugs(protease inhibitors) with the same result. Death.
Wouldn't it make infinitely better sense to have the medical and molecular biological communities seriously study the thousands of HIV + patients who are totally asymptomatic and have not had any of these agents? Wouldn't that be a great place to start? John Burgin, DDS
1:55 PM
Hi Bianca
Thank you for this link.
Sooty Mangabey SIV response
1)The immune response to early viremia directed towards the lymphatic organs where high viremia occurs through macrophages,is for a limited period.As a result,the damage inflicted to lymphatic tissue by way of fibrosis is minimal.The overall health of the immune organs like lymph system and thymus where progenitor immune cells mature and differentiate is very important for preservation of immunecompetency.
2)After the initial viremia and high limited period immune response,the subsequent immune response is not intense.Perhaps,there may not be a situation of high proinflammatory immune status as seen HIV in humans.This perhaps explains slow replication( or latency of the virus in sooty mangabey).Some kind of a homeostasis is achieved with viral set point and immune health with respect to cd4 counts.
3)Perhaps,this can be explained by a process of effective immune regulation that happens in sooty mangabey.Foxp3 protein and cd25 subset of cd4 cells will be involved in this regulation.
Progressive immune deficiency in HIV is composite effect of CTL death(apoptosis and necrosis)and irreversible damage caused to immune organs by frequent immune activations.This also explains cytopenia in AIDS patients.
Immune regulatory strategies will mimic sooty mangabey response to sivinfection.
This is going be the holy grail in HIV
Johns suggestion to study non-progressors is very relevant.May be many of them have an innate immune regulation maintaining homeostasis and good health.Perhaps drugs directed towards "HIV harm reduction" will prolong the life of non progressors by not letting them progress to opportunistic infections and aids!
Sunil Bhaskaran
11:25 PM
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