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Mayo Clinic Announces
Possible AIDS Breakthrough
(onlinedatingmagazine.com -
April 28, 2004) Mayo Clinic researchers have found
a way to revive immunity in mice that have abnormal
or deficient immune systems. The discovery may lead
to a means of restoring immunity to individuals with
immunodeficiency diseases such as AIDS and cancer.
Also, because the research involves an existing therapy,
application may be possible in the near future.
The research team, led by Mayo Clinic immunologists
Marilia Cascalho, M.D., Ph.D., and Jeffrey Platt, M.D.,
report in this month’s Journal of Immunology
that B cells, the lymphocytes that produce antibodies,
help to generate T cells, the lymphocytes that fight
viruses and tumors.
“Previously, it was thought that B cells and
T cells, two components of immunity produced by the
lymphatic tissues, develop independently until they
eventually came together to fight microbes or to eliminate
infected cells in the body,” says Dr. Cascalho. “Now
we know that the B cells and the immunoglobulin that
they produce can help reconstitute immunity by promoting
the development of T cells.”
For immunity to
work it is crucial that there are enough T cells
and also that the T cells be diverse so they are able
to
respond to many different threats. B cells help to
make the T cells in the body diverse. Immunoglobulin
is a specialized protein that acts as an antibody.
Diversity
of lymphocyte receptors is thought to be the key to
immunity. A cell’s receptor is the
portion that makes it selectively bind with another
substance. The more diverse T cell receptors are, the
more likely it is T cells of the appropriate specificity
will be present to combat today’s sophisticated
viruses or evasive bacteria. This flexibility and corresponding
T cell receptor diversity are absent in patients with
immunodeficiency diseases and in some who have cancer
or receive cancer treatment. AIDS patients, for example,
may have very few T cells and those T cells they have
may not be diverse. The report by Dr. Cascalho’s
group suggests it may be possible to boost T cell numbers
and diversity by administration of gamma globulin or
B cells. Gamma globulin is a protein portion of blood
rich in antibodies that is made from pooled human blood
and injected as one form of immunotherapy.
“By
understanding how the body produces T cell diversity
in this way, we believe it may have direct impact on
many patients whose immune defenses have been compromised,” says
Dr. Platt. “There was no way we knew of that
this part of the immune system could build itself back
up. Now, we think that this is a way.” Whether
B cells contribute to a diversity of T cells through
means other than immunoglobulin isn’t known. A Second Possible Approach
Dr. Cascalho theorizes that the gamma globulin might
also counter autoimmunity. In some cases autoimmune
diseases, such as arthritis, arise because the body
lacks the diverse T cells needed to control immune
responses. She says gamma globulin could promote
the production of new T cells which can control the
overreacting T cells that attack the body’s
healthy cells. In this way, clinicians may be able
to alter immunity by skewing or redirecting the focus
of the body’s misdirected immune response.
While she says this theory is untested, it could
be one more method for controlling autoimmunity.
Accelerated Human Trials
The next step is to test the current findings in clinical
trials. This process may take less time than usual
because gamma globulin is approved by the U.S. Food
and Drug Administration for other uses. That will
allow the researchers to retarget it to verify their
discovery in humans. “Because of this availability,
we should expect to see some results in a matter
of a few years, rather than in a decade or more,” says
Dr. Cascalho. The researchers want to discover whether
all or only part of the immunoglobulin molecule is
essential to “jump start” T cell production.
If they can identify the critical portion of the
molecule, it might be manufactured at less cost than
the expensive fully-constituted human immunoglobulin.
In addition to the AIDS virus, immune deficiency
can be caused by a range of autoimmune diseases,
old age, and can be a result of chemotherapy treatments
for cancer.
Study Details
Researchers transferred B cells or gamma globulin from
normal mice to those with limited T cell diversity
and found that the thymus generated new T cells with
increased diversity. However, administration of monoclonal
B cells or monoclonal immunoglobulin did not result
in production of more diverse T cells, proving that
diverse B cells and or immunoglobulin were essential
to restore immunity.
The lead author of the research article, predoctoral
student Cristina Joao, worked with Dr. Cascalho, who
heads the laboratory, and Dr. Platt, who heads the
research program in which the work was carried out.
Others involved in the study included Brenda M. Ogle,
Ph.D., and Carlota Gay-Rabinstein, M.D.
[Cristina João, Brenda M. Ogle, Carlota Gay-Rabinstein,
Jeffrey L. Platt, and Marilia Cascalho. (2004). B cell-dependent
TCR diversification. J. Immunology 172: 4709 – 4716.]
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