<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">clinmed</journal-id><journal-title-group><journal-title xml:lang="ru">Клиническая медицина</journal-title><trans-title-group xml:lang="en"><trans-title>Clinical Medicine (Russian Journal)</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">0023-2149</issn><issn pub-type="epub">2412-1339</issn><publisher><publisher-name>ООО «Медицинское информационное агентство»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.30629/0023-2149-2022-100-2-3-119-125</article-id><article-id custom-type="elpub" pub-id-type="custom">clinmed-361</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL INVESTIGATIONS</subject></subj-group></article-categories><title-group><article-title>Частота активации герпес-вирусных инфекций у реципиентов почечного трансплантата</article-title><trans-title-group xml:lang="en"><trans-title>Frequency of herpes virus infections activation in renal graft recipients</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Джумабаева</surname><given-names>Б. Т.</given-names></name><name name-style="western" xml:lang="en"><surname>Dzhumabaeva</surname><given-names>B. T.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Джумабаева Болдукыз Толгонбаевна — д-р мед. наук, ведущий научный сотрудник отделения полиорганной патологии и гемодиализа</p><p>125167, Москва</p></bio><bio xml:lang="en"><p>Dzhumabaeva Boldukyz T.</p><p>125167, Moscow</p></bio><email xlink:type="simple">bola.blood@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бирюкова</surname><given-names>Л. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Biryukova</surname><given-names>L. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>125167, Москва</p></bio><bio xml:lang="en"><p>125167, Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Капранов</surname><given-names>Н. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Kapranov</surname><given-names>N. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>125167, Москва</p></bio><bio xml:lang="en"><p>125167, Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тихомиров</surname><given-names>Д. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Tikhomirov</surname><given-names>D. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>125167, Москва</p></bio><bio xml:lang="en"><p>125167, Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Туполева</surname><given-names>Т. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Tupoleva</surname><given-names>T. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>125167, Москва</p></bio><bio xml:lang="en"><p>125167, Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Давыдова</surname><given-names>Ю. О.</given-names></name><name name-style="western" xml:lang="en"><surname>Davydova</surname><given-names>Yu. O.</given-names></name></name-alternatives><bio xml:lang="ru"><p>125167, Москва</p></bio><bio xml:lang="en"><p>125167, Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гальцева</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Gal'ceva</surname><given-names>I. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>125167, Москва</p></bio><bio xml:lang="en"><p>125167, Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>National Research Center of Hematology</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>25</day><month>06</month><year>2022</year></pub-date><volume>100</volume><issue>2-3</issue><fpage>119</fpage><lpage>125</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Джумабаева Б.Т., Бирюкова Л.С., Капранов Н.М., Тихомиров Д.С., Туполева Т.А., Давыдова Ю.О., Гальцева И.В., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Джумабаева Б.Т., Бирюкова Л.С., Капранов Н.М., Тихомиров Д.С., Туполева Т.А., Давыдова Ю.О., Гальцева И.В.</copyright-holder><copyright-holder xml:lang="en">Dzhumabaeva B.T., Biryukova L.S., Kapranov N.M., Tikhomirov D.S., Tupoleva T.A., Davydova Y.O., Gal'ceva I.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.clinmedjournal.com/jour/article/view/361">https://www.clinmedjournal.com/jour/article/view/361</self-uri><abstract><p>У реципиентов почечного трансплантата на фоне иммуносупрессивной терапии в течение первого года после трансплантации наблюдается развитие вирусных инфекций, приводящих к дисфункции и потерe трансплантата. В настоящей работе приведены результаты исследований субпопуляций Т-лимфоцитов у реципиентов почечного трансплантата до и после операции, а также у доноров крови (контрольная группа). Показано влияние отклонений в Т-клеточном звене иммунитета на развитие цитомегаловирусной (ЦМВ) и Эпштейна–Барр-вирусной (ВЭБ) инфекции в посттрансплантационном периоде. В исследование включено 19 реципиентов почечного трансплантата, медиана возраста 43 года, мужчин — 14, женщин — 5. Контрольную группу составили 20 здоровых доноров крови. Через месяц после трансплантации аллогенной почки (ТАП) на фоне индукционной (метилпреднизолон, базиликсимаб) и базисной (преднизолон, такролимус, микофенолата мофетил) иммуносупрессивной терапии, обнаружены маркеры репликации ЦМВ у 10 (53%) и ВЭБ у 7 (36,9%) пациентов. Профиль обнаруженных маркеров ЦМВ и/или ВЭБ в подавляющем большинстве случаев соответствовал реактивации эндогенного вируса. ЦМВ- и/или ВЭБ-инфекция после ТАП развивались у пациентов, у которых до ТАП была значительно снижена доля лимфоцитов, абсолютное количество наивных CD4+ и СD8+, эффекторных CD4+ клеток памяти, регуляторных T-клеток (CD4+/CD25+/CD127–) по сравнению с контрольной группой. При ВЭБ-инфекции до ТАП определялось также достоверное снижение количества CD3+, абсолютного количества CD4+ и CD8+, увеличение доли центральных CD8+ клеток памяти по сравнению с контрольной группой. Таким образом, частота реактивации вирусной инфекции в первые месяцы после ТАП зависит не только от проводимой иммуносупрессивной терапии, но и от изменений субпопуляций Т-лимфоцитов до ТАП. Данные изменения могут быть учтены для профилактики возникновения вирусной инфекции после трансплантации почки.</p></abstract><trans-abstract xml:lang="en"><p>Immunosuppressive treatment during the first year after renal transplantation leads to viral infection development in recipients, and graft dysfunction up to its loss. This original article gives data on comparison of T-lymphocytes subsets in healthy blood donors and renal graft recipients before and one month after transplantation. The influence of T-cell immunity impairment on CMV- and EBV-infection emergence were evaluated. 19 renal graft recipients were included in the study (average age — 43, m/f ratio — 14/5). 20 healthy blood donors were used as controls. A month after transplantation during induction (Methylprednisolone and Basiliximab) and basis (Prednisolone, Tacrolimus, Mycophenolate mofetil) therapy 10 (53%) patients had makers of CMV replication and 7 (36.9%) patients had markers of EBV replication. The majority of CMV- and EBV-positive patients proved reactivation of endogenous CMV and EBV (not primary infection). All patients, subsequently positive for CMV and EBV, demonstrated T-cells subpopulations discount before transplantation, such as a decrease in the total number of lymphocytes and absolute number of naïve CD4+ and СD8+ cells, effector memory CD4+ cells, T-regulatory cells (CD4+/CD25+/CD127–) in comparison to the control group. EBV-positive patients also showed the reduction of CD3+, absolute number of CD4+ and CD8+, but central memory CD8+ cells increased in comparison to the control group. Viral reactivation rate during first month after renal transplantation depends not only on immunosuppressive regimen but on T-cells subsets disproportions before graft. These indicators could be taken into account for viral infection expectancy.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>цитомегаловирус</kwd><kwd>вирус Эпштейна–Барр</kwd><kwd>трансплантация почки</kwd><kwd>субпопуляция Т-лимфоцитов</kwd><kwd>Т-регуляторные клетки</kwd></kwd-group><kwd-group xml:lang="en"><kwd>cytomegalovirus</kwd><kwd>Epstein–Barr virus</kwd><kwd>kidney transplantation</kwd><kwd>T-lymphocyte subpopulation</kwd><kwd>T-regulatory cells</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Горяйнов В.А., Каабак М.М., Бабенко Н.Н., Агуреева Л.И., Морозова М.М. и др. Влияние цитомегаловируса на результаты трансплантации почек. Клиническая медицина. 2015;11:44–47.</mixed-citation><mixed-citation xml:lang="en">Goriainov V.A. Kaabak M.M., Babenko N.N., Agureeva LI, Morozova M.M. et al. Effect of cytomegalovirus on the results of kidney transplantation. Clinical medicine. [Klinicheskaya medicina]. 2015;11:44–47. (In Russian)</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Инфекции в трансплантологии. Под ред. С.В. Готье. М., Триада, 2010.</mixed-citation><mixed-citation xml:lang="en">Infections in transplantology. Ed. S.V. Got'e. M., Triada, 2010. (In Russian)</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Садовский Д.Н., Калачик О.В., Юнис Н., Лавринюк Р.П., Амвросьева Т.В., Гринкевич П.И. и др. Цитомегаловирусная инфекция при трансплантации почки. Медицинский журнал. 2012;4:85–88.</mixed-citation><mixed-citation xml:lang="en">Sadovskij D.N., Kalachik O.V., Yunis N., Lavrinyuk R.P., Amvros'eva T.V., Grinkevich P.I. et al. Cytomegalovirus in fection in kidney transplantation. Medical Journal. [Medicinskiy zhurnal]. 2012;4:85–88(In Russian)</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Razonable R.R. Cytomegalovirus in Solid Organ Transplantation. Am. J. Transplant. 2013;13:93–106.</mixed-citation><mixed-citation xml:lang="en">Razonable R.R. Cytomegalovirus in Solid Organ Transplantation. Am. J. Transplant. 2013;13:93–106.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Lee S., Affandi J.S., Irish A.B., Price P. Cytomegalovirus infection alters phenotypes of different γδ T-cell subsets in renal transplant recipients with long-term stable graft function. J. Med Virol.2017;89(8):1442–1452. DOI: 10.1002/jmv.24784</mixed-citation><mixed-citation xml:lang="en">Lee S., Affandi J.S., Irish A.B., Price P. Cytomegalovirus infection alters phenotypes of different γδ T-cell subsets in renal transplant recipients with long-term stable graft function. J. Med Virol.2017;89(8):1442–1452. DOI: 10.1002/jmv.24784</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Makwana N., Foley B., Fernandez S., Lee S., Irish A., Pircher H., Price P. CMV drives the expansion of highly functional memory T cells expressing NK-cell receptors in renal transplant recipients. Eur. J. Immunol. 2017;47(8):1324–1334. DOI: 10.1002/eji.201747018</mixed-citation><mixed-citation xml:lang="en">Makwana N., Foley B., Fernandez S., Lee S., Irish A., Pircher H., Price P. CMV drives the expansion of highly functional memory T cells expressing NK-cell receptors in renal transplant recipients. Eur. J. Immunol. 2017;47(8):1324–1334. DOI: 10.1002/eji.201747018</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Páez-Vega A., Poyato A., Rodriguez-Benot A., Guirado L., Fortún J., Len O. et al. Analysis of spontaneous resolution of cytomegalovirus replication after transplantation in CMV-seropositive patients with pretransplant CD8+IFNG+ response. Antiviral. Res. 2018;155:97–105. DOI: 10.1016/j.antiviral.2018.05.006</mixed-citation><mixed-citation xml:lang="en">Páez-Vega A., Poyato A., Rodriguez-Benot A., Guirado L., Fortún J., Len O. et al. Analysis of spontaneous resolution of cytomegalovirus replication after transplantation in CMV-seropositive patients with pretransplant CD8+IFNG+ response. Antiviral. Res. 2018;155:97–105. DOI: 10.1016/j.antiviral.2018.05.006</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Tanné C., Roy P., Frobert É., Duncan A., Laurent A., Cochat P. Cytomegalovirus infection in the first year after pediatric kidney transplantation. Nephrol. Ther. 2018;S1769–7255(18)30116–0. DOI: 10.1016/j.nephro.2018.04.003</mixed-citation><mixed-citation xml:lang="en">Tanné C., Roy P., Frobert É., Duncan A., Laurent A., Cochat P. Cytomegalovirus infection in the fi rst year after pediatric kidney transplantation. Nephrol. Ther. 2018;S1769–7255(18)30116–0. DOI: 10.1016/j.nephro.2018.04.003</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Fernández-Ruiz M., Giménez E., Vinuesa V., Ruiz-Merlo T., Parra P., Amat P., Montejo M. et al. Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment. Clin. Microbiol. Infect. 2018;25:S1198–743X(18)30441-5. DOI: 10.1016/j.cmi.2018.05.010</mixed-citation><mixed-citation xml:lang="en">Fernández-Ruiz M., Giménez E., Vinuesa V., Ruiz-Merlo T., Parra P., Amat P., Montejo M. et al. Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment. Clin. Microbiol. Infect. 2018;25:S1198–743X(18)30441-5. DOI: 10.1016/j.cmi.2018.05.010</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Matz M., Fabritius K., Liu J., Lorkowski C., Brakemeier S., Unterwalder N. et al. Conversion to Belatacept based regimen does not change T-cell phenotype and function in renal transplantation. Transpl. Immunol. 2015;33(3):176–84. DOI: 10.1016/j.trim.2015.10.002</mixed-citation><mixed-citation xml:lang="en">Matz M., Fabritius K., Liu J., Lorkowski C., Brakemeier S., Unterwalder N. et al. Conversion to Belatacept based regimen does not change T-cell phenotype and function in renal transplantation. Transpl. Immunol. 2015;33(3):176–84. DOI: 10.1016/j.trim.2015.10.002</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Jamil B., Nicholls K., Becker G.J., Walker R.G. Impact of acute rejection therapy on infections and malignancies in renal transplant recipients. 1999;68(10):1597–603.</mixed-citation><mixed-citation xml:lang="en">Jamil B., Nicholls K., Becker G.J., Walker R.G. Impact of acute rejection therapy on infections and malignancies in renal transplant recipients. 1999;68(10):1597–603.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Gottschalk S., Rooney C.M., Heslop H.E. Post-transplant lymphoproliferative disorders. Ann. Rev. Med. 2005;56:29–44. DOI: 1146/annurev.med.56.082103.104727</mixed-citation><mixed-citation xml:lang="en">Gottschalk S., Rooney C.M., Heslop H.E. Post-transplant lymphoproliferative disorders. Ann. Rev. Med. 2005;56:29–44. DOI: 1146/annurev.med.56.082103.104727</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Rasche L., Kapp M., Einsele H., Mielke S. EBV-induced post transplant lymphoproliferative disorders: a persisting challenge in allogeneic hematopoetic SCT. Bone Marrow Transplant. 2014;49(2):163–7. DOI: 10.1038/bmt.2013.96</mixed-citation><mixed-citation xml:lang="en">Rasche L., Kapp M., Einsele H., Mielke S. EBV-induced post transplant lymphoproliferative disorders: a persisting challenge in allogeneic hematopoetic SCT. Bone Marrow Transplant. 2014;49(2):163–7. DOI: 10.1038/bmt.2013.96</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Burns D.M., Tierney R., Shannon-Lowe C., Croudace J., Inman C., Abbotts B. et al. Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event. 2015;126(25):2665–2675. DOI: 10.1182/blood-2015-08-665000</mixed-citation><mixed-citation xml:lang="en">Burns D.M., Tierney R., Shannon-Lowe C., Croudace J., Inman C., Abbotts B. et al. Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event. 2015;126(25):2665–2675. DOI: 10.1182/blood-2015-08-665000</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Klein U., Rajewsky K., Küppers R. Human immunoglobulin (Ig) M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J. Exp. Med. 1998;188(9):1679–1689.</mixed-citation><mixed-citation xml:lang="en">Klein U., Rajewsky K., Küppers R. Human immunoglobulin (Ig) M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J. Exp. Med. 1998;188(9):1679–1689.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Fox CP., Shannon-Lowe C., Rowe M. Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations. 2011;2:8. DOI: 10.1186/2042-4280-2-8</mixed-citation><mixed-citation xml:lang="en">Fox CP., Shannon-Lowe C., Rowe M. Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations. 2011;2:8. DOI: 10.1186/2042-4280-2-8</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Calattini S., Sereti I., Scheinberg P., Kimura H., Childs R. W., Cohen J.I. Detection of EBV genomes in plasmablasts/plasma cells and non-B cells in the blood of most patients with EBV lymphoproliferative disorders by using Immuno-FISH. 2010;116(22):4546–59. DOI: 10.1182/blood-2010-05-285452</mixed-citation><mixed-citation xml:lang="en">Calattini S., Sereti I., Scheinberg P., Kimura H., Childs R. W., Cohen J.I. Detection of EBV genomes in plasmablasts/plasma cells and non-B cells in the blood of most patients with EBV lymphoproliferative disorders by using Immuno-FISH. 2010;116(22):4546–59. DOI: 10.1182/blood-2010-05-285452</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Bouvy A.P., Klepper M., Kho M.M., Boer K., Betjes M.G., Weimar W., Baan C.C. The impact of induction therapy on the homeostasis and function of regulatory T cells in kidney transplant patients. Nephrol. Dial. Transplant. 2014;29(8):1587–97. DOI: 10.1093/ndt/gfu079</mixed-citation><mixed-citation xml:lang="en">Bouvy A.P., Klepper M., Kho M.M., Boer K., Betjes M.G., Weimar W., Baan C.C. The impact of induction therapy on the homeostasis and function of regulatory T cells in kidney transplant patients. Nephrol. Dial. Transplant. 2014;29(8):1587–97. DOI: 10.1093/ndt/gfu079</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Safinia N., Scotta C., Vaikunthanathan T., Lechler., Lombardi G. Regulatory T сells: serious contenders in the promise for immunological tolerance in transplantation. Front Immunol. 2015;6:438. DOI: 10.3389/fimmu.2015.00438</mixed-citation><mixed-citation xml:lang="en">Safinia N., Scotta C., Vaikunthanathan T., Lechler., Lombardi G. Regulatory T сells: serious contenders in the promise for immunological tolerance in transplantation. Front Immunol. 2015;6:438. DOI: 10.3389/fimmu.2015.00438</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Read S., Malmstrom V., Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+) CD4(+) regulatory cells that control intestinal infl ammation. J. Exp. Med. 2000;192(2):295–302. DOI: 10.1084/jem.192.2.295</mixed-citation><mixed-citation xml:lang="en">Read S., Malmstrom V., Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+) CD4(+) regulatory cells that control intestinal infl ammation. J. Exp. Med. 2000;192(2):295–302. DOI: 10.1084/jem.192.2.295</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Qureshi O.S., Zheng Y., Nakamura K., Attridge K., Manzotti C., Schmidt E.M. et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011;332(6029):600–3. DOI: 10.1126/science.1202947</mixed-citation><mixed-citation xml:lang="en">Qureshi O.S., Zheng Y., Nakamura K., Attridge K., Manzotti C., Schmidt E.M. et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011;332(6029):600–3. DOI: 10.1126/science.1202947</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Takahashi T., Tagami T., Yamazaki S., Uede T., Shimizu J., Sakaguchi N. et al. Immunologic self-tolerance maintained by CD25(+) CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 2000;192(2):303–10. DOI: 10.1084/jem.192.2.303</mixed-citation><mixed-citation xml:lang="en">Takahashi T., Tagami T., Yamazaki S., Uede T., Shimizu J., Sakaguchi N. et al. Immunologic self-tolerance maintained by CD25(+) CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 2000;192(2):303–10. DOI: 10.1084/jem.192.2.303</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Fahlen L., Read S., Gorelik L., Hurst S.D., Coffman R.L., Flavell R.A. et al. T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells. J. Exp. Med; 2005:201(5):737–46. DOI: 10.1084/jem.20040685</mixed-citation><mixed-citation xml:lang="en">Fahlen L., Read S., Gorelik L., Hurst S.D., Coffman R.L., Flavell R.A. et al. T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells. J. Exp. Med; 2005:201(5):737–46. DOI: 10.1084/jem.20040685</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Powrie F., Carlino J., Leach M.W., Mauze S., Coffman R.L. A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells. J. Exp. Med. 1996;183(6):2669–74. DOI: 10.1084/jem.183.6.2669</mixed-citation><mixed-citation xml:lang="en">Powrie F., Carlino J., Leach M.W., Mauze S., Coffman R.L. A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells. J. Exp. Med. 1996;183(6):2669–74. DOI: 10.1084/jem.183.6.2669</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Hara M., Kingsley CI., Niimi M., Read S., Turvey S.E., Bushell A.R. et al. IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J. Immunol. 2001;166(6):3789–96. DOI: 10.4049/jimmunol.166.6.3789</mixed-citation><mixed-citation xml:lang="en">Hara M., Kingsley CI., Niimi M., Read S., Turvey S.E., Bushell A.R. et al. IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J. Immunol. 2001;166(6):3789–96. DOI: 10.4049/jimmunol.166.6.3789</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Collison L.W., Workman C.J., Kuo T.T., Boyd K., Wang Y., Vignali K.M. et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature.2007;450(7169):566–9. DOI: 10.1038/nature06306</mixed-citation><mixed-citation xml:lang="en">Collison L.W., Workman C.J., Kuo T.T., Boyd K., Wang Y., Vignali K.M. et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature.2007;450(7169):566–9. DOI: 10.1038/nature06306</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Gondek D.C., Lu L.F., Quezada S.A., Sakaguchi S., Noelle R.J. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J. Immunol. 2005;174(4):1783–6. DOI: 10.4049/jimmunol.174.4.1783</mixed-citation><mixed-citation xml:lang="en">Gondek D.C., Lu L.F., Quezada S.A., Sakaguchi S., Noelle R.J. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J. Immunol. 2005;174(4):1783–6. DOI: 10.4049/jimmunol.174.4.1783</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Grossman W.J., Verbsky J.W., Tollefsen B.L., Kemper C., Atkinson J.P., Ley T.J. Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells. Blood. 2004;104(9):2840–8. DOI: 10.1182/blood-2004-03-0859</mixed-citation><mixed-citation xml:lang="en">Grossman W.J., Verbsky J.W., Tollefsen B.L., Kemper C., Atkinson J.P., Ley T.J. Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells. Blood. 2004;104(9):2840–8. DOI: 10.1182/blood-2004-03-0859</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Deaglio S., Dwyer K.M., Gao W., Friedman D., Usheva A., Erat A. et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 2007;204(6):1257–65. DOI: 10.1084/jem.20062512</mixed-citation><mixed-citation xml:lang="en">Deaglio S., Dwyer K.M., Gao W., Friedman D., Usheva A., Erat A. et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 2007;204(6):1257–65. DOI: 10.1084/jem.20062512</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Wood K.J., Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat. Rev. Immunol. 2003;3(3):199–210.10.1038/nri1027</mixed-citation><mixed-citation xml:lang="en">Wood K.J., Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat. Rev. Immunol. 2003;3(3):199–210.10.1038/nri1027</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
