The viral context instructs the redundancy of costimulatory pathways in driving CD8+ T cell expansion
- Leiden University Medical Center, Netherlands
- Helmholtz-Zentrum für Infektionsforschung GmbH, Germany
- University of Freiburg, Germany
Abstract
Signals delivered by costimulatory molecules are implicated in driving T cell expansion. The requirements for these signals, however, vary from dispensable to essential in different infections. We examined the underlying mechanisms of this differential T cell costimulation dependence and found that the viral context determined the dependence on CD28/B7-mediated costimulation for expansion of naive and memory CD8+ T cells, indicating that the requirement for costimulatory signals is not imprinted. Notably, related to the high-level costimulatory molecule expression induced by LCMV, CD28/B7-mediated costimulation was dispensable for accumulation of LCMV-specific CD8+ T cells because of redundancy with the costimulatory pathways induced by TNF receptor family members (i.e. CD27, OX40, and 4-1BB). Type I IFN signaling in viral-specific CD8+ T cells is slightly redundant with costimulatory signals. These results highlight that pathogen-specific conditions differentially and uniquely dictate the utilization of costimulatory pathways allowing shaping of effector and memory antigen-specific CD8+ T cell responses.
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Ethics
Animal experimentation: Animal experiments were approved by the Animal Experiments Committee of the LUMC (reference numbers: 12006, 13150, 14046 and 14066) and performed according to the recommendations and guidelines set by the LUMC and by the Dutch Experiments on Animals Act that serves the implementation of 'Guidelines on the protection of experimental animals' by the Council of Europe.
Copyright
© 2015, Welten et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The viral context instructs the redundancy of costimulatory pathways in driving CD8+ T cell expansion
eLife 4:e07486.
https://doi.org/10.7554/eLife.07486
