Highlights- Interferon mediated initial immune response results in
prolonged inflammation of CD8 T cells.
- Blocking this interferon 1 allows the CD8 T
cells to re-energize and mount a more specific response
against HIV.
- The renewed CD8 T cells response and anti-retroviral therapy will lower viral load much
more effectively.
An immune response has
always been considered necessary in fighting infections, it may no longer be
the same, according to scientists from UCLA. It was found that a protein which
elicits an immune response should be blocked to help combat
HIV, in a study
published in the
Journal of Clinical
Investigation.
Blocking Protein That Activates Immune Response Found Effective Against HIV Infection
Interferon 1
Blocking Interferon 1
could speed up immune response against HIV viral infection and lead
to their suppression in individuals who have a chronic infection with HIV and
are under anti-viral drug therapy. This is the first study that shows the
importance of interferon 1 in the destruction of immune response in HIV
positive people.
‘Modulating immune response against HIV virus could be an effective treatment.’
Senior author of the
study, Dr. Scott Kitchen who is an associate professor of medicine in the
department of hematology/oncology (David Geffen School of Medicine at UCLA)
said, "This finding is completely counterintuitive, because many
believe that the more interferon at work, the better. We show that the type of
interferon being produced during chronic stages of HIV infection has
detrimental effects on the body's ability to fight off HIV and other types of
infection or cancer and could actually be contributing to accelerated HIV
disease."
HIV Infection
HIV infection leads to
an immune response in the body towards the virus in the blood. This immune response that
occurs initially is called seroconversion and the infected individual will show
signs of illness at this stage and test positive for HIV. After this, the virus
will remain in the host body for many years without any apparent effect on the
health of the individual. However, the virus, at this stage, would have caused
damage to the immune system.
In an immune response to
any infection, the CD4 T
cells are the first line of defense. These immune cells are
also called helper cells as they signal for another type of cells called the
CD8 T
cells. The HIV virus destroys the CD4 T cells
by activating an immune response triggered by Interferon 1. The virus mutates
numerous times to evade being detected by the CD8 T cells.
The prolonged period of inflammation results in immune exhaustion.
Blocking Interferon 1
The scientists in this
study postulated that blocking interferon 1 would not lead to the extended
period of inflammation that occurs in an HIV infection.
This would let the CD8 T
cells recover from the initial attack and will provide time to
let them regain in strength.
The scientists believe
that
the renewed CD8 T cells would be able to mount a more
specific response to the virus and these cells, along with the anti-retroviral
therapy, will aid in lowering the viral load significantly.
Humanized Mice
The scientists used HIV infected
humanized mice
-mice that had immune cells, thymus tissue and bone marrow
from humans. When the interferon 1 was blocked using antibodies, the immune
cells reverted from a state of exhaustion. When the immune cells next mounted
an immune response, it was more specifically targeted at the HIV virus
and, together with the
anti-retroviral
therapy, lead to a faster decline in immune cells.
Dr. Kitchen stated that
these studies that involved blocking the immune system, resulted in a more
potent attack of the virus. The scientists also stated that these experiments
were carried out on humanized mice and not on humans, therefore further tests
are needed to validate the results.
Dr. Anjie Zhen, a
postdoctoral scholar working with UCLA AIDS Institute adds a word of caution
when resorting to therapy based on blocking Interferon 1. It could lead to a
host of other issues that could occur when the immune function is lowered.
Interferon 1 and CD8 T
Cells Response
Interferon 1 was the
first interferon to be discovered and this interferon is called 'viral'
interferon as they can be induced directly by the virus. The other type of
interferon would require specific receptor binding to T cells and natural
killer (NK) cells.
The Interferon 1 gets
activated by the viral nuclei and proteins. Studies on mice that do not have
the interferon 1 have shown that the mice can survive in a pathogen free
environment but cannot cope with viral attack.
Type 1 interferon is
found to greatly increase the co-stimulatory effect by binding
to the IFN1R on the CD8 T cells, greatly increasing their
secretion. It has a co-stimulatory effect and drives immune response of T
cells. T-cells that are generated late are indirectly sensitized by interferon
1.
The current study, that
focuses on suppressing the interferon mediated immune response would aid in
blocking the immune response temporarily to provide sufficient time for the CD8 T
cells to recover. However, it could make the individual at increased risk for
infections, but careful monitoring and care could overcome the reduction in
immunity.
References:- Anjie Zhen, Valerie Rezek, Cindy Youn, Brianna Lam, Nelson Chang, Jonathan Rick, Mayra Carrillo, Heather Martin, Saro Kasparian, Philip Syed, Nicholas Rice, David G. Brooks, Scott G. Kitchen. Targeting type I interferon-mediated activation restores immune function in chronic HIV infection. Journal of Clinical Investigation, 2016; DOI: 10.1172/JCI89488
- CD4+ T cell depletion in HIV infection: mechanisms of immunological failure - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729334/)
- Type 1 Interferons and Antiviral CD8 T-Cell Responses - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252364/)
- Protein that activates immune response harms body's ability to fight HIV - (https://www.eurekalert.org/pub_releases/2016-12/uoc--pta122216.php)
Source-Medindia
Careers
