V. G. Blinova, Y. A. Gladilina, D. D. Eliseeva, T. A. Lobaeva, D. D. Zhdanov
{"title":"体外转化调节性T细胞与同一供体未刺激细胞相比抑制活性增加","authors":"V. G. Blinova, Y. A. Gladilina, D. D. Eliseeva, T. A. Lobaeva, D. D. Zhdanov","doi":"10.1134/S1990750822030039","DOIUrl":null,"url":null,"abstract":"<div><div><h3>\n <b>Abstract</b>—</h3><p>Regulatory T cells CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>СD127<sup>low</sup> (Tregs) play a key role in the maintenance of tolerance to autoantigens, inhibit the function of effector T and B lymphocytes, and provide a balance between effector and regulatory arms of immunity. Patients with autoimmune diseases are characterized by decreased Treg numbers and impaired suppressive activity. Replacement therapy with autologous Tregs transformed ex vivo could restore the destroyed balance of the immune system. We developed a method for the cultivation of Treg precursor cells. Using this method, we were able to grow up to 300−400 million Treg cells from 50 mL of peripheral blood during a week. In this study, we demonstrated that 90−95% of ex vivo-transformed Tregs had the phenotype CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>СD127<sup>low</sup> and increased the transcription of the <i>FoxP3</i> and <i>Helios</i> genes. Ex vivo-transformed Tregs were characterized by increased demethylation of the <i>FoxP3</i> promoter and activation of the proliferation gene markers cyclin B1, Ki67 and LGALS 1. Ex vivo-transformed Tregs had increased suppressive activity, and up to 80–90% of these cells secreted the cytokines TNFα and IFNγ. Our data suggest that ex vivo-transformed autologous Tregs have genetic, immunophenotypic and functional characteristics of regulatory T cells. In the future, they can be used for adoptive immunotherapy of autoimmune diseases and inhibition of transplantation immunity.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"16 3","pages":"225 - 237"},"PeriodicalIF":0.6000,"publicationDate":"2022-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Increased Suppressor Activity of Ex Vivo Transformed Regulatory T Cells in Comparison with Unstimulated Cells of the Same Donor\",\"authors\":\"V. G. Blinova, Y. A. Gladilina, D. D. Eliseeva, T. A. Lobaeva, D. D. Zhdanov\",\"doi\":\"10.1134/S1990750822030039\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div><h3>\\n <b>Abstract</b>—</h3><p>Regulatory T cells CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>СD127<sup>low</sup> (Tregs) play a key role in the maintenance of tolerance to autoantigens, inhibit the function of effector T and B lymphocytes, and provide a balance between effector and regulatory arms of immunity. Patients with autoimmune diseases are characterized by decreased Treg numbers and impaired suppressive activity. Replacement therapy with autologous Tregs transformed ex vivo could restore the destroyed balance of the immune system. We developed a method for the cultivation of Treg precursor cells. Using this method, we were able to grow up to 300−400 million Treg cells from 50 mL of peripheral blood during a week. In this study, we demonstrated that 90−95% of ex vivo-transformed Tregs had the phenotype CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>СD127<sup>low</sup> and increased the transcription of the <i>FoxP3</i> and <i>Helios</i> genes. Ex vivo-transformed Tregs were characterized by increased demethylation of the <i>FoxP3</i> promoter and activation of the proliferation gene markers cyclin B1, Ki67 and LGALS 1. Ex vivo-transformed Tregs had increased suppressive activity, and up to 80–90% of these cells secreted the cytokines TNFα and IFNγ. Our data suggest that ex vivo-transformed autologous Tregs have genetic, immunophenotypic and functional characteristics of regulatory T cells. In the future, they can be used for adoptive immunotherapy of autoimmune diseases and inhibition of transplantation immunity.</p></div></div>\",\"PeriodicalId\":485,\"journal\":{\"name\":\"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry\",\"volume\":\"16 3\",\"pages\":\"225 - 237\"},\"PeriodicalIF\":0.6000,\"publicationDate\":\"2022-08-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry\",\"FirstCategoryId\":\"2\",\"ListUrlMain\":\"https://link.springer.com/article/10.1134/S1990750822030039\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","FirstCategoryId":"2","ListUrlMain":"https://link.springer.com/article/10.1134/S1990750822030039","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Increased Suppressor Activity of Ex Vivo Transformed Regulatory T Cells in Comparison with Unstimulated Cells of the Same Donor
Abstract—
Regulatory T cells CD4+CD25+FoxP3+СD127low (Tregs) play a key role in the maintenance of tolerance to autoantigens, inhibit the function of effector T and B lymphocytes, and provide a balance between effector and regulatory arms of immunity. Patients with autoimmune diseases are characterized by decreased Treg numbers and impaired suppressive activity. Replacement therapy with autologous Tregs transformed ex vivo could restore the destroyed balance of the immune system. We developed a method for the cultivation of Treg precursor cells. Using this method, we were able to grow up to 300−400 million Treg cells from 50 mL of peripheral blood during a week. In this study, we demonstrated that 90−95% of ex vivo-transformed Tregs had the phenotype CD4+CD25+FoxP3+СD127low and increased the transcription of the FoxP3 and Helios genes. Ex vivo-transformed Tregs were characterized by increased demethylation of the FoxP3 promoter and activation of the proliferation gene markers cyclin B1, Ki67 and LGALS 1. Ex vivo-transformed Tregs had increased suppressive activity, and up to 80–90% of these cells secreted the cytokines TNFα and IFNγ. Our data suggest that ex vivo-transformed autologous Tregs have genetic, immunophenotypic and functional characteristics of regulatory T cells. In the future, they can be used for adoptive immunotherapy of autoimmune diseases and inhibition of transplantation immunity.
期刊介绍:
Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.