Enhanced CD8 T Cell Responses through GITR-Mediated Costimulation Resolve Chronic Viral Infection

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The ability of the immune system to rapidly respond to a viral infection is a prerequisite for the survival of an individual. The immediate reaction of innate immune cells and the subsequent response of antigen-specific lymphocytes is usually effective for rapid neutralization and removal of the invading virus. Yet, such protective immune responses need to be well controlled, as they can cause severe tissue damage that may disable the host more than the infection itself. One way that has evolutionarily been proven effective to deal with this balancing act between protective immunity and prevention of immunopathology is to render virus-specific T cells “exhausted” when the virus cannot be eradicated and the host becomes chronically infected. Exhausted T cells progressively lose their ability to kill other cells and produce different cytokines. The benefit of this exhausted state of anti-viral immunity is that it induces less tissue damage, but the downside is obviously less efficient control over the viral infection. Many immunotherapeutic and vaccination strategies against chronic viral infections are currently dedicated to overcome the exhausted state of the virus-specific T cells and thereby clear the virus. However, the accompanying risk is an exaggerated immune response with overt immunopathology. Here we describe in a mouse model that enhanced triggering through the costimulatory molecule GITR on T cells is able to provide protection upon viral infection and clear an otherwise persistent virus, but importantly without the development of collateral damage due to immunopathology. We show that GITR-mediated costimulation enhances a protective CD8 T cell response, for which CD4 T cell help is required. Our study provides new insights in how a particular costimulatory pathway can be utilized to boost anti-viral immunity, which is highly relevant for the development of safe immunotherapeutic strategies against chronic viral infections in humans.

Vyšlo v časopise: Enhanced CD8 T Cell Responses through GITR-Mediated Costimulation Resolve Chronic Viral Infection. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004675
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004675

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