TY - JOUR TI - The viral context instructs the redundancy of costimulatory pathways in driving CD8+ T cell expansion AU - Welten, Suzanne PM AU - Redeker, Anke AU - Franken, Kees LMC AU - Oduro, Jennifer D AU - Ossendorp, Ferry AU - Čičin-Šain, Luka AU - Melief, Cornelis JM AU - Aichele, Peter AU - Arens, Ramon A2 - Rath, Satyajit VL - 4 PY - 2015 DA - 2015/08/11 SP - e07486 C1 - eLife 2015;4:e07486 DO - 10.7554/eLife.07486 UR - https://doi.org/10.7554/eLife.07486 AB - 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 lymphocytic choriomeningitis virus (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. KW - t cell KW - costimulation KW - viral infection JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -