RGD Reference Report - Superagonistic CD28 Protects against Renal Ischemic Injury by Expansion of Regulatory T-Cell.

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Superagonistic CD28 Protects against Renal Ischemic Injury by Expansion of Regulatory T-Cell.
Authors:	Liang, Yiran Li, Yan Kuang, Qing Ding, Xiaoqiang Wei, Zheng Fang, Yi
Citation:	Liang Y, etal., Am J Nephrol. 2017;45(5):389-399. doi: 10.1159/000470918. Epub 2017 Mar 29.
RGD ID:	14975115
Pubmed:	PMID:28355607 (View Abstract at PubMed)
DOI:	DOI:10.1159/000470918 (Journal Full-text)
BACKGROUND: Regulatory T (Treg) cells are a highly suppressive subset of CD4+ lymphocytes and have recently been proved to be crucial to suppress the inflammatory responses of ischemic kidney injury. CD28 superagonists (CD28sa) are monoclonal antibodies that preferentially expand Treg cells without a T-cell receptor and a costimulatory signal. This study aims to test the protection and discover the mechanisms of CD28sa treatment against renal ischemia-reperfusion (IR) injury (IRI). METHODS: Male C57BL/6N mice were treated with CD28sa via peritoneal injection (0.1 mg) 6 days before the induction of IRI, or with 18-min ischemic precondition (IPC). IRI was induced by bilateral clamping of renal pedicles for 35 min followed by reperfusion. The role of Treg expansion in renal protection conferred by CD28sa treatment was examined using anti-CD25 antibody. RESULTS: CD28sa treatment alone significantly increased the percentage of Treg cells in the spleen (18.10 ± 2.00 vs. 6.64 ± 0.86%, p < 0.01), peripheral blood (16.43 ± 5.94 vs. 2.57 ± 1.09%, p < 0.01), and kidney (2.69 ± 0.90 vs. 0.53 ± 0.14%, p < 0.01) of C57BL/6N mice 6 days after the administration. Mice pretreated with CD28sa or IPC had less renal injury at 24 h after IRI with attenuation of renal tubular damage and lower serum creatinine compared with the mice that underwent renal IRI alone. The number of infiltrating macrophages in the kidney and IFN-γ secreting CD4+ T cells in peripheral blood were diminished in the CD28sa-IR group and the IPC-IR group. The renal protection bestowed by CD28sa or IPC was abolished by anti-CD25 antibody administration. CONCLUSIONS: Treg expansion induced by CD28sa ameliorated renal IRI.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
IFNG	Human	Kidney Reperfusion Injury	treatment	ISO	Ifng (Mus musculus)		RGD
Ifng	Rat	Kidney Reperfusion Injury	treatment	ISO	Ifng (Mus musculus)		RGD
Ifng	Mouse	Kidney Reperfusion Injury	treatment	IEP			RGD

Objects Annotated

Genes (Rattus norvegicus)

Ifng (interferon gamma)

Genes (Mus musculus)

Ifng (interferon gamma)

Genes (Homo sapiens)

IFNG (interferon gamma)

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Superagonistic CD28 Protects against Renal Ischemic Injury by Expansion of Regulatory T-Cell.