Details

Autor(en) / Beteiligte

• Rajasalu, Tarvo
• Brosi, Helen
• Schuster, Cornelia
• Spyrantis, Andreas
• Boehm, Bernhard Otto
• Chen, Lieping
• Reimann, Jorg
• Schirmbeck, Reinhold

Titel

Deficiency in B7-H1 /PD-1 coinhibition triggers ancreatic [beta]-cell destruction by insulin-specific, murine CD8 T-cells

Ist Teil von

• Diabetes (New York, N.Y.), 2010-08, Vol.59 (8), p.1966

Ort / Verlag

American Diabetes Association

Erscheinungsjahr

2010

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.sup.-/-], [PD-1.sup.-/-] 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.sup.-/-] or [PD-1.sup.-/-] 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.