Blockade of the Interaction Between PD-1 and PD-L1 Accelerates Graft Arterial Disease in Cardiac Allografts
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
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 γ (IFN-γ) and tumor necrosis factor α 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-γ stimulation. Sensitized splenocytes increased SMC proliferation, and anti–PD-L1 mAb in combination with IFN-γ 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.
- Received May 31, 2004.
- Accepted August 23, 2004.