Wednesday’s Track A sessions
featured three areas of basic science research:
- The role of humoral immune responses;
- The immune tissues and cells which harbour HIV
(viral reservoir).
- The impact of anti-HIV therapies on the immune
system and how the immune responses against HIV may recover after significant virus
suppression with anti-HIV therapy.
Several presentations have
focused on the role of cellular immunity, the arm of the immune system that directly
attacks infected cells. Humoral immunity (antibody responses) is the arm of the immune
system that targets infections outside of cells. HIV exists both inside (cell-associated)
and outside of cells. The following are highlights from presentations:
- The antibody response in HIV infection has been
critically evaluated. The lesson we learned from other viral infections teaches us that
antibodies are important both in preventing infections and controlling diseases. Sometimes
cellular immunity alone is sufficient to control or prevent infections. Other times
humoral immunity can do the trick. Other viral infections teach us that sometimes both
arms of the immune system must be called to action simultaneously – this is what we
need in HIV infection.
- Many antibodies are produced in HIV infected
people. Those that block the virus from entering a cell are a subject of much interest.
These antibodies are called neutralizing antibodies. Studies are showing that HIV-infected
pregnant women who have high levels of neutralizing antibodies to HIV appear to be less
likely to transmit HIV to their child. Strategies to enhance the production of these
antibodies may prove useful in preventing transmission of HIV from mother-to-child.
- HIV-specific antibodies were found in the genital
tract of HIV exposed yet uninfected sex workers in Africa. The antibodies were not found
in their blood, however. These immune responses, localized in the genital tract, are one
factor that may explain why these women remain persistently HIV uninfected.
Throughout the course of HIV
infection, the virus is harboured in various immune compartments. In Tuesday’s
summary we provided an overview of how HIV lurks in resting CD4+ T cells, which represents
a reservoir for the virus and can prevent the anti-HIV effects of both the immune system
and anti-HIV drugs. There are other reservoirs for HIV. These include deeper immune
compartments such as the lymph nodes. Cell types other than CD4+ T cells, macrophages and
dendritic cells, may also act as viral reservoirs. These reservoirs do not necessarily
hide the virus from therapies and the immune system in the same way that resting CD4+ T
cells do. Many cells and tissues, other than those of the immune system, can be infected
with HIV besides the sites highlighted here. For example, reservoirs of HIV include the
testis and brain.
- Lymph nodes are immune environments where cells in
tissues are highly organized into a complex network. Many immune responses are initiated
in the lymph nodes, which is the place where information is processed and cells respond
accordingly. HIV also is harboured in this immune compartment. Throughout the course of
HIV disease, the cells in lymph nodes become disorganized and thus the communication
between many cell types is damaged. Proper communication between cells and the ability of
the lymph node to respond to foreign antigen in the lymph nodes, is highly dependent on an
intact structure. Many groups have shown that the structure of the lymph nodes is
increasingly disturbed throughout the course of HIV disease. Surprising and encouraging
are results from recent studies which show that treatment with potent anti-HIV therapy can
lead to restoration of the lymph node structure. Cells previously destroyed and
disorganized, after therapy, re-appear and reassemble into an organized network.
Dendritic cells and macrophages
can be likened to the scouts of the immune system army. The cells ingest HIV and present
proteins from the virus to CD4+ T cells in order to initiate immune recognition and
response against the virus. In other words, these are important cells (called antigen
presenting cells) that interact with CD4+ T cells in order to initiate cellular and
humoral immune responses. Macrophages are a reservoir for HIV, in fact, the most commonly
sexually transmitted strain of HIV (the NSI virus summarized in Monday’s session
highlights) preferentially infects these cells. It is a subject of some controversy as to
whether or not dendritic cells are infected by HIV.
- Dendritic cells are excellent reservoirs for HIV
as they are very large and thus many CD4+ T cells can come in contact and interact with
them. For HIV, this is a benefit as it facilitates the virus’ ability to transfer
from a dendritic cell to the many CD4+ T cells that come in contact with it.
- Macrophages may also harbour virus and can
transmit HIV to a CD4+ T cell during the process of protein presentation. Additionally,
macrophages may be a key cell in carrying HIV across the blood-brain barrier leading to
the establishment of HIV infection in brain tissue. Virus can thrive in a macrophage for a
long period of time and not be targeted by immune responses.
While we have previously
highlighted information on the immune response and immune consequences of potent anti-HIV
therapy, additional information was presented during wednesday’s session. Largely
this information confirmed and strengthened previous presentations at this forum.
Wednesday’s presentations expanded the panorama of the immune landscape.
- A number of studies demonstrate that people
treated with potent anti-HIV therapy very early after infection, within days, appear to
restore HIV-specific cellular immune responses. It is not yet clear if these same
responses can be restored in people who have established HIV infection. One exception
observed was in a singular individual receiving a drug combination including hydroxyurea.
It is not known if this restored response was due to therapy with this combination,
however.
- Studies have confirmed that people treated with
potent anti-HIV therapy do have a number of improvements in immune responses. These
include restored immune responses to common infections such as candida (yeast) and
cytomegalovirus (CMV). While some responses are restored, others are not. Some speculate
that it may simply take longer than three years (the amount of time potent therapy has
been available) in order to see demonstrated improvements in a large spectrum of immune
responses. Others are proceeding with therapeutic strategies to re-educating the immune
system, using vaccines, to improve the immune responses that are not restored. These might
include HIV vaccines.
- Treating with an immune chemical, IL-2, in
combination with potent anti-HIV therapy has been shown to dramatically increase CD4+ cell
counts. When to initiate IL-2 therapy, at which CD4+ T cell level, remains unclear. IL-2
has been used more extensively among people with higher (above 350) CD4+ T cell counts.
Small studies suggest it may also improve CD4+ T cell number in people with lower counts
as well. (Note: IL-2 therapy is not without side effects and people and their providers
should educate themselves before experimenting with this therapy!)
|
back
want more?
