ABSTRACT
Notch signaling pathway plays a key role in the development and fate of T lymphocytes and B lymphocytes,and may be a therapeutic target in alloimmunity.In this paper,we reviewed the functions of Notch signaling pathway in the activation and differentiation of T lymphocyte and formation of memory T cell subsets,and its role in the alloimmunity.Selective inhibition of multiple Notch receptors and ligands in a solid organ transplantation model can successfully modulate the allograft immune response and influence the balance between immune effector cells and regulatory cells,which suggests that selective targeting of Notch signaling pathway is expected to become a new immunomodulatory therapy for organ transplantation.
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.
Subject(s)
Animals , Female , Humans , Mice , Allografts , Cell Proliferation , Cell Survival , Enzyme-Linked Immunosorbent Assay , Graft Survival , Hand , Interleukin-2 , Lymphocyte Culture Test, Mixed , Necrosis , Nerve Growth Factor , Skin , Tissue Donors , TransplantsABSTRACT
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.