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Women who are pregnant or using synthetic
progesterone birth control injections have a
conspicuous vulnerability to certain infections
including malaria, Listeria, HIV, and herpes simplex
virus.
A new research report appearing in the March 2013
issue of the Journal of Leukocyte Biology offers
strong evidence for a possible explanation: the
progesterone receptor, a pregnancy hormone sensor,
targets a part of the immune system responsible for
protection against these and other invaders. In
addition to helping explain why some women are more
vulnerable to certain infections, it also sheds
light on why some autoimmune diseases, notably
rheumatoid arthritis and multiple sclerosis, often
go into remission during pregnancy.
"We hope that continued work in this area will
ultimately yield better approaches to the prevention
of immunological complications of pregnancy, safer
and more effective forms of hormonal birth control
and novel biological targets for the treatment of
autoimmune diseases," said Grant C. Hughes, M.D., a
researcher involved in the work from the Division of
Rheumatology and Department of Immunology at the
University of Washington in Seattle, WA.
To make their discovery, scientists used two groups
of mice. The first group had a mutated progesterone
receptor, or PR gene, which rendered the mice's
bodies incapable of sensing progesterone through PR
(PR knockout mice). The second group was comprised
of normal mice.
After various forms of immunization, antibody
responses were tracked. When compared to normal mice,
PR knockout mice produced much higher antibody
levels, but only in response to forms of
immunization requiring T cells, a cell type that
normally boosts antibody production by B cells. This
prompted a closer look at B and T cells from the PR
knockout mice. The researcher saw that when
stimulated in the test tube, knockout B cells showed
normal, if not slightly less, antibody production
compared to controls.
On the other hand, knockout T cells stimulated in
the test tube showed a conspicuous over-production
of interferon-gamma, an inflammatory molecule
involved in fighting off pregnancy-associated
pathogens and in shaping protective antibody
responses.
Adding progesterone to the test tube blocked
interferon-gamma in normal T cells, but not in PR
knockout T cells. This suggests that progesterone
suppresses interferon gamma in T cells through their
PR.
To sort out which aspects of the abnormal antibody
responses in PR knockout mice were due to T cells,
researchers immunized two groups of normal mice, one
transplanted with responder T cells from PR knockout
donors, the other with responder T cells from normal
donors.
Just like in PR knockout mice, normal mice
transplanted with PR knockout responder T cells
showed much higher antibody levels than normal mice.
"Pregnancy and hormones have long been known to
influence immune responses, but these processes have
been poorly understood, said John Wherry, Ph.D.,
Deputy Editor of the Journal of Leukocyte Biology. "This
new work is significant for two reasons. First, the
identification of progesterone receptors as a
mechanism of immune modulation during pregnancy
sheds light on the pregnancy-immune phenomenon, and
second, these studies define a potentially new
target to modulate autoimmunity and immune-mediated
problems during pregnancy."
For more information
Grant C. Hughes, Edward A. Clark, and Alan H. Wong.
The intracellular progesterone receptor regulates
CD4+ T cells and T cell-dependent antibody responses.
J Leukoc Biol March 2013 93:369-375, doi:10.1189/jlb.1012491
;
http://www.jleukbio.org/content/93/3/369.abstract
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Federation of American Societies for Experimental
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