Immune tolerance agent

An immune tolerance and preparation technology, which is applied in the application field of hepatocyte growth factor in the immune tolerance of organ transplantation, can solve the problems of the relationship between damage and effective regeneration, and the unclear molecular regulation mechanism, so as to prolong the survival of receptors and broaden the application. range effect

Pending Publication Date: 2019-05-21
THE FIRST AFFILIATED HOSPITAL OF ARMY MEDICAL UNIV
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  • Application Information

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Problems solved by technology

However, the current research on the relationship between HGF and T lymphocytes in the immune system such as CD8 + The relationship between immune regulation between CTL to promote effective regeneration after injury and the molecular regulation mechanism of establishing immune tolerance after organ transplantation are not yet clear and have not been reported in the literature

Method used

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Experimental program
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Effect test

Embodiment 1

[0030] Fluorescence detection found liver tissue stem cells (Liver-NG2 + Stem cells) express HGF ( figure 1 , A); in allogeneic and xenogeneic liver transplantation, transfer of Liver-NG2 + Hepatic local HGF secretion of stem cells is higher ( figure 1 , B). The above experimental results show that tissue stem cells secrete HGF.

Embodiment 2

[0032] The biological effects of HGF are mainly mediated through the tyrosine kinase receptor cMet, which is also the only known HGF receptor. In order to determine whether the immune tolerance of Liver-NG2 positive stem cells in xenograft liver transplantation is related to the HGF signaling pathway, we used Chinese hamsters (Lewis-Chinese Hamster) and Lewis rats to conduct xenograft liver transplantation studies, and the transplantation was transfused intravenously at the same time. Liver-NG2 cells (1×10 6 / 0.5mL / Rat), it was found that the average survival period of rats in the model group was between 2.5-3 days; while the survival period of rats treated with Liver-NG2+ stem cells exceeded 14 days ( figure 2 , A), better than the FK506 treatment group. Using specific antibody to block cMet, the only receptor of HGF, significantly weakened the tolerance effect, indicating that the immune tolerance effect of Liver-NG2+ stem cells is through the secretion of HGF. Local dete...

Embodiment 3

[0034] HGF induces immune tolerance and CD8 + CTL lymphocyte activity is closely related. HGF directly inhibits the proliferative response of cytotoxic T lymphocytes (CD8+ T cells). We used magnetic bead negative selection method to sort and purify CD8 + T lymphocytes ( image 3 , A), CD8 was found + T lymphocytes express a large number of HGF only receptor cMet ( image 3 , B-D), further using HGF and sorting to purify CD8 + The co-culture of T lymphocytes found that the sorting and purification of T lymphocytes in transplanted recipients showed that HGF significantly reduced the proliferation activity of CD8+ T lymphocytes, and was accompanied by a decrease in the level of pro-inflammatory cytokine IL-2, while the anti-inflammatory cytokine IL- 10 level increase ( image 3 , E). The above results indicated that CD8 expressing HGF receptor + T lymphocytes proliferate after receiving HGF signals resulting in reduced activity.

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Abstract

The invention discloses application of a hepatic growth factor (HGF) in the preparation of an organ transplantation immune tolerance agent. The main function is that HGF is expressed in a CD8-cytotoxic-T-lymphocyte (CTL) surface cMet/FAS molecular coupling mode (CD8<+>CTL<cMet/FAS>) through regulating to induce apoptosis of CTL. The CD8<+>T CTL is a major lymphocyte population which attacks heterologous target organs or target antigens. Therefore, stem cells (or drugs) which give HGF or secrete HGF in the allogeneic or xenogeneic organ transplantation process can significantly prolong the survival of transplanted organs and recipients. The application not only broadens the application range of HGF preparations or HGF-secreting cells (or drugs), but also provides a new immunosuppressive treatment drug for clinical organ transplantation application.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of hepatocyte growth factor in immune tolerance of organ transplantation. Background technique [0002] Organ disease or failure such as end-stage liver disease (End-stage liver diseases ESLD) is a major disease in my country. Various reasons can lead to organ failure such as car accidents, chronic diseases, myocardial infarction, etc. These basically relate to all age groups, such as young and middle-aged people (20-50 years old) and old people who are in their prime of life. Taking the liver as an example, there are more than 2,500,000 patients with end-stage liver disease in the world, and there were about 65,000 ESLD patients in my country in 2004, showing a rapid growth trend in recent years, with a high mortality rate. At present, the only strategy for the basic or failed treatment of organs in medicine is organ transplantation. However, immunosuppressants such...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61K35/545A61P37/06A61P29/00
CPCA61K35/545A61K38/18A61P29/00A61P37/06
Inventor 白莲花张宏宇
Owner THE FIRST AFFILIATED HOSPITAL OF ARMY MEDICAL UNIV
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