4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses.
4-1BB (CD137) is a costimulatory molecule expressed on activated T cells and interacts with 4-1BB ligand (4-1BBL) on APCs. To investigate the role of 4-1BB costimulation for the development of primary immune responses, 4-1BBL-deficient (4-1BBL-/-) mice were infected with lymphocytic choriomeningitis virus (LCMV). 4-1BBL-/- mice were able to generate CTL and eliminate acute LCMV infection with normal kinetics, but CD8 T cell expansion was 2- to 3-fold lower than in wild-type (+/+) mice. In the same mice, virus-specific CD4 Th and B cell responses were minimally affected, indicating that 4-1BB costimulation preferentially affects CD8 T cell responses. This result contrasts with our earlier work with CD40L-deficient (CD40L-/-) mice, in which the CD8 T cell response was unaffected and the CD4 T cell response was markedly impaired. When both 4-1BBL- and B7-dependent signals were absent, CD8 T cell expansion was further reduced, resulting in lower CTL activity and impairing their ability to clear LCMV. Altogether, these results indicate that T cells have distinct costimulatory requirements: optimal CD8 responses require 4-1BBL-dependent interactions, whereas CD4 responses are minimally affected by 4-1BB costimulation, but require CD40-CD40L and B7-dependent interactions.
Tan
J T
JT
The Carlos and Marguerite Mason Transplantation Biology Research Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA.
Whitmire
J K
JK
Ahmed
R
R
Pearson
T C
TC
Larsen
C P
CP
D053330:4-1BB Ligand; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D018122:B7-1 Antigen / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D007111:Immunity, Cellular / Q000235:genetics; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008231:Lymphopenia / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D053330:4-1BB Ligand; D018122:B7-1 Antigen; D018106:CD28 Antigens; D008024:Ligands; C505975:Tnfsf9 protein, mouse; D014409:Tumor Necrosis Factor-alpha