Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Rajasalu, T. et al.

Deficiency in B7-H1 (PD-L1)/PD-1 coinhibition triggers pancreatic beta-cell destruction by insulin-specific, murine CD8 T-cells.

OBJECTIVE: RIP-B7.1 mice expressing the costimulator molecule B7.1 (CD80) on pancreatic beta-cells are a well established model to characterize preproinsulin-specific CD8 T-cell responses and experimental autoimmune diabetes (EAD). Different immunization strategies could prime preproinsulin-specific CD8 T-cells in wild-type C57BL/6 (B6) mice, but did not induce diabetes. We tested whether altering the B7-H1 (PD-L1) coinhibition on pancreatic beta-cells can reveal a diabetogenic potential of preproinsulin-specific CD8 T-cells. RESEARCH DESIGN AND METHODS: DNA-based immunization and adoptive T-cell transfers were used to characterize the induction of preproinsulin-specific CD8 T-cell responses and EAD in RIP-B7.1, B6, B7-H1(-/-), PD-1(-/-) or bone marrow chimeric mice. RESULTS: Preproinsulin-specific CD8 T-cells primed in B6 mice revealed their diabetogenic potential after adoptive transfer into congenic RIP-B7.1 hosts. Furthermore, preproinsulin-specific CD8 T-cells primed in anti-B7-H1 antibody-treated B6 mice, or primed in B7-H1(-/-) or PD-1(-/-) mice induced EAD. Immunization of bone marrow chimeric mice showed that deficiency of either B7-H.1 in pancreatic beta-cells or of PD-1 in autoreactive CD8 T-cells induced EAD. CONCLUSIONS: An imbalance between costimulator (B7.1) and coinhibitor (B7-H1) signals on pancreatic beta-cells can trigger pancreatic beta-cell-destruction by preproinsulin-specific CD8 T-cells. Hence, regulation of the susceptibility of the beta-cells for a preproinsulin-specific CD8 T-cell attack can allow or suppress EAD.[1]

References

Deficiency in B7-H1 (PD-L1)/PD-1 coinhibition triggers pancreatic beta-cell destruction by insulin-specific, murine CD8 T-cells. Rajasalu, T., Brosi, H., Schuster, C., Spyrantis, A., Boehm, B.O., Chen, L., Reimann, J., Schirmbeck, R. Diabetes (2010) [Pubmed]

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