The viral context instructs the redundancy of costimulatory pathways in driving CD8(+) T cell expansion.
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.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.
Suzanne P M
SP
Welten
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.
Anke
A
Redeker
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.
Kees L M C
KL
Franken
Department for Vaccinology/Immune Aging and Chronic Infection, Helmholtz-Zentrum für Infektionsforschung GmbH, Braunschweig, Germany.
Jennifer D
JD
Oduro
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.
Ferry
F
Ossendorp
Department for Vaccinology/Immune Aging and Chronic Infection, Helmholtz-Zentrum für Infektionsforschung GmbH, Braunschweig, Germany.
Luka
L
Čičin-Šain
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.
Cornelis J M
CJ
Melief
Department of Medical Microbiology and Hygiene, Institute of Immunology, University of Freiburg, Freiburg, Germany.
Peter
P
Aichele
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.
Ramon
R
Arens
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology*
D036341:Intercellular Signaling Peptides and Proteins
T cells; costimulation; immunology; infectious disease; microbiology; mouse; viral infection