Turning Off the Immune System May Turn on Protection Against HIV

저자：   업로드：2017-07-12  조회수：

    Even though HIV rates declined 18% between 2008 and 2014, 1.1 million people in the US are living with the infection. Part of that is because HIV is treatable, but not curable.

    HIV attacks the very cells of the immune system that should kill off the infection, and our bodies don't do a good job of fighting the virus. But, new research from the University of Colorado suggests a way we might be able to get the immune system to develop antibodies to HIV.

    The human immune system has a built in failsafe to ensure that we don’t normally produce antibodies that attack our own tissues. The failsafe, known as immune tolerance, ensures that any B cells that might produce self-reactive broadly neutralizing antibodies (bnAbs) are eliminated in the bone marrow, or if the B cells do reach the circulation they are suppressed so that they can’t mature into antibody-secreting plasma cells.

    Work in mice by a team at the University of Colorado, School of Medicine now suggests that human immunodeficiency virus 1 (HIV-1) exploits immune tolerance to prevent the production of broadly neutralizing antibodies (bnAbs) that can target the viral Env protein and destroy the virus, because the same antibodies would also recognize epitopes on the body’s own histone H2A. The team, led by Raul M. Torres, Ph.D., professor of immunology and microbiology at the University of Colorado, School of Medicine, has found that mice with weakened immune tolerance due genetic defects or drug treatment readily produce broadly neutralizing antibodies that can eliminate multiple strains of HIV-1.

    “We think this may reflect an example of molecular mimicry where HIV-1 Env has evolved to mimic an epitope on histone H2A as a mechanism of immune camouflage," Prof. Torres suggests.

    Human patients with the autoimmune disorder systemic lupus erythematosus (SLE) are known to demonstrate a lower incidence of HIV-1 infection, and this is thought to be because they produce self-reactive antibodies that can also neutralize HIV-1. To investigate this a bit further in a mouse model, Dr. Torres’ team looked first at animals with a genetic defect that causes symptoms similar to SLE. When the animals were injected with alum, an adjuvant used in vaccines to trigger antibody secretion, they started to produce antibodies that neutralize HIV-1.

    Production of antibodies that could neutralize HIV-1 was also associated with increased levels of a self-reactive antibody targeting histone H2A. “ … autoimmune-prone strains of mice treated with alum produce HIV-1–neutralizing anti-bodies, and this activity correlates with increased anti-H2A IgM autoantibody titers,” the authors note in their published paper in the