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 an d 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 choriomeningi tis 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-speci fic 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 wa s 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 indic ate that T cells have distinct costimulatory requirements: optimal CD8 resp onses require 4-1BBL-dependent interactions, whereas CD4 responses are mini mally affected by 4-1BB costimulation, but require CD40-CD40L and B7-depend ent interactions.