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'Pep Talk' can Revive Exhausted Immune Cells

by Sheela Philomena on December 16, 2011 at 12:46 PM
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 'Pep Talk' can Revive Exhausted Immune Cells

Immune cells exhausted from infections can be revived by the introduction of fresh cells that act like coaches giving a pep talk, reveals study.

Chronic infections by viruses such as HIV or hepatitis C eventually take hold because they wear the immune system out, a phenomenon that immunologists describe as exhaustion.

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Senior author Rafi Ahmed's laboratory has extensive experience studying mice infected with lymphocytic choriomeningitis virus (LCMV). Immune responses against LCMV are driven by CD8 or "killer" T cells, which destroy virus-infected cells in the body.

Merely a few weeks after exposure to LCMV, the mice develop a chronic infection that their immune systems cannot shake off, similar to when humans are infected by viruses like HIV and hepatitis C.
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Rachael Aubert, Ahmed and their team from Emory Vaccine Center examined what happened to mice chronically infected with lymphocytic choriomeningitis virus (LCMV) when they infused CD4 or "helper" T cells from uninfected mice.

After the infusion, the CD8 cells in the infected mice revived and the levels of virus in their bodies decreased by a factor of four after a month. Like coaches encouraging a tired athlete, the helper cells drove the killer cells that were already in the infected mice to emerge from exhaustion and re-engage.

The cell-based treatment was especially effective when combined with an antibody that blocks the molecule PD-1, which appears on exhausted T cells and inhibits their functioning. The antibody against PD-1 helps the exhausted T cells to revive, and enhances the function of the helper cells as well: the combination reduced viral levels by roughly ten-fold, and made the virus undetectable in some mice.

"We have not seen this sharp of a reduction in viral levels in this system before," Alice Kamphorst, co-author of the study, said.

The researchers found that the helper cells were all genetically engineered to recognize LCMV, a difference between mouse experiments and potential clinical application. However, it may be possible to remove helper T cells from a human patient and stimulate them so that all the cells that recognize a given virus grow.

"This is an active area of research and several laboratories are looking at how best to stimulate T cells and re-introduce them," she added.

The study has been published in Proceedings of the National Academy of Sciences Early Edition.

Source: ANI
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