The viral context instructs the redundancy of costimulatory pathways in driving CD8+ T cell expansion
Suzanne PM Welten,
Anke Redeker,
Kees LMC Franken,
Jennifer D Oduro,
Ferry Ossendorp,
Luka Čičin-Šain,
Cornelis JM Melief,
Peter Aichele,
Ramon Arens
Affiliations
Suzanne PM Welten
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
Anke Redeker
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
Kees LMC Franken
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
Jennifer D Oduro
Department for Vaccinology/Immune Aging and Chronic Infection, Helmholtz-Zentrum für Infektionsforschung GmbH, Braunschweig, Germany
Ferry Ossendorp
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
Luka Čičin-Šain
Department for Vaccinology/Immune Aging and Chronic Infection, Helmholtz-Zentrum für Infektionsforschung GmbH, Braunschweig, Germany; Department for Virology, Medical School Hannover, Hannover, Germany
Cornelis JM Melief
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands; ISA Pharmaceuticals, Leiden, Netherlands
Peter Aichele
Department of Medical Microbiology and Hygiene, Institute of Immunology, University of Freiburg, Freiburg, Germany
Ramon Arens
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
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.
