Reprogramming T Cells

Effective T cell responses are critical for the control of viral infections. Failure to clear persistent viral infections like HIV, and Hepatitis B and C in humans or lymphocytic choriomeningitis virus (LCMV) in rodents can be caused by early loss of T cell activity due to depletion of this cell population. Following exposure to an antigen, T cells are prompted to increase in number, and to develop certain immune functions as well as the ability to remember and recognize certain antigens.

In a study appearing online on May 18 in advance of print publication in the June issue of the Journal of Clinical Investigation, David G. Brooks and colleagues from The Scripps Research Institute, La Jolla, California, show that this programming of T cells is alterable, even once the programming has begun, and is highly dependent on continuous signals from the antigen environment.

In the presence of persistent viral replication, these T cell responses are rapidly altered, making T cells unresponsive and allowing for unchecked viral persistence. Brooks et al. show that deletion of immunodominant T cells and functional inactivation can be prevented in vivo in mice during persistent LCMV infection, resulting in a more diverse virus-specific T cell repertoire and the long-term preservation of cytotoxic T lymphocyte responses.

The concept that T cell deletion and inactivation is neither an inevitable nor permanent consequence of persistent viral infection - that it is reversible - and that its reversal leads to control of viral infection, should have important implications for the future design of therapeutic approaches to resurrect T cell responses and treat persistent viral infections.

TITLE: Reprogramming of antiviral T cells prevents inactivation and restores T cell activity during persistent viral infection.

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