Alloimmune and Skin Allograft Responses in 4-1BB (CD137)-deficient Mice

ABSTRACT

BACKGROUND: The costimulatory molecule 4-1BB, a member of nerve growth factor receptor/tumor necrosis factor (NGFR/TNFR) super family, is involved in cell survival and death. METHODS: In this study, female C57BL/6 (H-2(b)) mice were used as a recipient, and DBA/2 (H-2(d)) as a donor to assess a mixed lymphocyte reaction (MLR) and CTL response in vitro, and skin graft survival. IL-2, IFN level was measured by ELISA. RESULTS: Mixed lymphocyte reaction (MLR) analysis showed that 4-1BB- deficient responder cells showed enhanced cellular proliferation over littermate controls. In contrast, IL-2 production was diminished only in 4-1BB knockout cultures. The IFN expression, on the other hand, was comparable between the groups. When female C57BL/6 (H-2(b)) mice were grafted with the trunk skin of DBA/2 (H-2d) mice, the in vivo tissue destruction of 4-1BB-deficient mice was not distinct from the normal littermates. CONCLUSION: These data suggest that 4-1BB is critical for the induction of alloreactive responses in vitro but 4-1BB alone could not change the course of skin rejection in vivo.