BACKGROUND: Programmed death-1 (PD-1), a member of the CD28 family, has been identified. PD-1 is involved in the negative regulation of some immune responses. We evaluated the role of PD-ligand 1 (PD-L1) in graft arterial disease (GAD) of cardiac allografts and in smooth muscle cells (SMCs). METHODS AND RESULTS: C57BL/6 murine hearts were transplanted into B6.C-H2<bm12>KhEg mice for examination of GAD. PD-L1 was expressed in SMCs of the thickened intima in the graft coronary arteries, and administration of anti-PD-L1 monoclonal antibody (mAb) enhanced the progression of GAD (luminal occlusion: 55+/-5.0% versus 9.8+/-4.3%, P<0.05). The expressions of interferon gamma (IFN-gamma) and tumor necrosis factor alpha of cardiac allografts were upregulated in response to anti-PD-L1 mAb treatment. In vitro, PD-L1 expression was induced in SMCs in response to IFN-gamma stimulation. Sensitized splenocytes increased SMC proliferation, and anti-PD-L1 mAb in combination with IFN-gamma stimulation increased this proliferation. CONCLUSIONS: The PD-L1 pathway regulates both the proliferation of SMCs and GAD. Thus, control of this interaction is a promising strategy for suppression of GAD.
BACKGROUND:Programmed death-1 (PD-1), a member of the CD28 family, has been identified. PD-1 is involved in the negative regulation of some immune responses. We evaluated the role of PD-ligand 1 (PD-L1) in graft arterial disease (GAD) of cardiac allografts and in smooth muscle cells (SMCs). METHODS AND RESULTS: C57BL/6 murine hearts were transplanted into B6.C-H2<bm12>KhEg mice for examination of GAD. PD-L1 was expressed in SMCs of the thickened intima in the graft coronary arteries, and administration of anti-PD-L1 monoclonal antibody (mAb) enhanced the progression of GAD (luminal occlusion: 55+/-5.0% versus 9.8+/-4.3%, P<0.05). The expressions of interferon gamma (IFN-gamma) and tumor necrosis factor alpha of cardiac allografts were upregulated in response to anti-PD-L1 mAb treatment. In vitro, PD-L1 expression was induced in SMCs in response to IFN-gamma stimulation. Sensitized splenocytes increased SMC proliferation, and anti-PD-L1 mAb in combination with IFN-gamma stimulation increased this proliferation. CONCLUSIONS: The PD-L1 pathway regulates both the proliferation of SMCs and GAD. Thus, control of this interaction is a promising strategy for suppression of GAD.
Authors: Katsunori Tanaka; Monica J Albin; Xueli Yuan; Kazuhiro Yamaura; Antje Habicht; Takaya Murayama; Martin Grimm; Ana Maria Waaga; Takuya Ueno; Robert F Padera; Hideo Yagita; Miyuki Azuma; Tahiro Shin; Bruce R Blazar; David M Rothstein; Mohamed H Sayegh; Nader Najafian Journal: J Immunol Date: 2007-10-15 Impact factor: 5.422
Authors: Jennifer E Cole; Tina J Navin; Amanda J Cross; Michael E Goddard; Lena Alexopoulou; Anuja T Mitra; Alun H Davies; Richard A Flavell; Marc Feldmann; Claudia Monaco Journal: Proc Natl Acad Sci U S A Date: 2011-01-10 Impact factor: 11.205
Authors: A M K Kaul; S Goparaju; N Dvorina; S Iida; K S Keslar; C A de la Motte; A Valujskikh; R L Fairchild; W M Baldwin Journal: Am J Transplant Date: 2015-01-12 Impact factor: 8.086
Authors: Johannes Wedel; Hironao Nakayama; Nora M Kochupurakkal; Josephine Koch; Michael Klagsbrun; Diane R Bielenberg; David M Briscoe Journal: Curr Opin Organ Transplant Date: 2017-02 Impact factor: 2.640