(Journal Article): The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice.
 
Ansari MJ, Salama AD, Chitnis T, Smith RN, Yagita H, Akiba H, Yamazaki T, Azuma M, Iwai H, Khoury SJ (Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA 02115, USA.)
 
IN: J Exp Med 2003; 198(1):63-69
Impact Factor(s) of J Exp Med: 14.588 (2004), 15.302 (2003), 15.34 (2001)

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ABSTRACT: Programmed death-1 (PD-1) receptor, an inhibitory costimulatory molecule found on activated T cells, has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated the role of this pathway in the development of autoimmune diabetes. PD-1 or PD-L1 but not PD-L2 blockade rapidly precipitated diabetes in prediabetic female nonobese diabetic (NOD) mice regardless of age (from 1 to 10-wk-old), although it was most pronounced in the older mice. By contrast, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade induced disease only in neonates. Male NOD mice also developed diabetes after PD-1-PD-L1 pathway blockade, but NOR mice, congenic to NOD but resistant to the development of diabetes, did not. Insulitis scores were significantly higher and frequency of interferon gamma-producing GAD-reactive splenocytes was increased after PD-1-PD-L1 pathway blockade compared with controls. Interestingly, PD-L1 but not PD-L2 was found to be expressed on inflamed islets of NOD mice. These data demonstrate a central role for PD-1-PD-L1 interaction in the regulation of induction and progression of autoimmune diabetes in the NOD mouse and provide the rationale to develop new therapies to target this costimulatory pathway in this disease.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Yadav D, Sarvetnik N. Costimulation and Pancreatic Autoimmunity: The PD-1/PD-L Conundrum. Rev Diabetic Stud 2006. 3: 6-10.
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