Инфекция и иммунитет. 2013; 3: 327-334
АНАЛИЗ СУБПОПУЛЯЦИЙ Т-ХЕЛПЕРОВ ПЕРИФЕРИЧЕСКОЙ КРОВИ БОЛЬНЫХ ХРОНИЧЕСКИМ ВИРУСНЫМ ГЕПАТИТОМ С, ЭКСПРЕССИРУЮЩИХ ХЕМОКИНОВЫЕ РЕЦЕПТОРЫ CXCR3 И CCR6 И АКТИВАЦИОННЫЕ МАРКЕРЫ CD38 И HLA-DR
https://doi.org/10.15789/2220-7619-2013-4-327-334Аннотация
Резюме. Адекватный адаптивный иммунный ответ при вирусных инфекциях зависит от Т-хелперных субпопуляций лимфоцитов и привлечения специфических Т-клеток в очаг инфекции. Целью исследования была оценка изменений состава субпопуляций Т-хелперов, несущих на поверхности хемокиновые рецепторы CXCR3 и CCR6 и активационные маркеры CD38 и HLA-DR, в периферической крови больных хроническим вирусным гепатитом С (n = 19) и практически здоровых доноров (n = 24). Содержание субпопуляций определяли методом проточной цитофлюориметрии с использованием комбинации моноклональных антител: HLA-DR-FITC/CD38-PE/CD3-ECD/CCR6-PE-Cy7/CXCR3-APC/CD4-APC-Cy7. Установлено сниженное количество CD38+ Т-хелперов и повышенное CXCR3 и CCR6 экспрессирующих Т-хелперов, в частности субпопуляции CD3+CD4+CXCR3+CCR6+ клеток. Показана значимость сочетанного определения комбинаций хемокиновых рецепторов CXCR3 и CCR6 и активационных маркеров CD38 и HLA-DR по сравнению с их раздельным анализом при хроническом гепатите С.
Список литературы
1. Арсентьева Н.А., Семенов А.В., Тотолян А.А. Роль полиморфизма генов цитокинов при вирусном гепатите С // Инфекция и иммунитет. — 2012. — Т. 2, № 4. — С. 687–698. Arsent`eva N.A., Semenov A.V., Totolian A.A. Rol` polimorfizma genov tsitokinov pri virusnom gepatite S [The role of cytokine gene polymorphism in hepatitis C virus infection]. Infektsiya i immunitet — Infection and Immunity, 2012, vol. 2, no. 4, pp. 687–698.
2. Вирусные гепатиты в Российской Федерации. Аналитический обзор. 8 выпуск / Под ред. В.И. Покровского, А.Б. Жебруна. — СПб.: ФБУН НИИЭМ имени Пастера, 2011. — 116 с. Virusnye gepatity v Rossiyskoy Federatsii. Analiticheskiy obzor. 8 vypusk (Pod red. V.I. Pokrovskogo, A.B. Zhebruna) [Viral hepatitis in Russian Federation. Analytical review. Issue 8 (Ed. Pokrovskiy V.I., Zhebrun A.B.)]. St. Petersburg Pasteur Institute, 2011. 116 p.
3. Жданов К.В., Гусев Д.А., Чирский B.C., Сысоев К.А., Якубовская Л.А., Шахманов Д.М., Тотолян А.А. Хроническая HCV-инфекция и экспрессия мРНК СС-хемокинов и их рецепторов // Журнал микробиологии, эпидемиологии и иммунобиологии. — 2008. — № 4. — С. 73–78. Zhdanov K.V., Gusev D.A., Chirskiy B.C., Sysoev K.A., Yakubovskaya L.A., Shakhmanov D.M., Totolian A.A. Hronicheskaya HCV-infektsiya i ekspressiya mRNK SS-khemokinov i ikh retseptorov [Chronic HCV infection and mRNA expression of CC-chemokines and their receptors]. Zhurnal mikrobiologii, epidemiologii i immunobiologii — Journal of Microbiology, Epidemiology and Immunobiology, 2008, vol. 4, pp. 73–78.
4. Сысоев К.А., Чухловин А.Б., Тотолян А.А. Диагностическая роль определения хемокинов и их рецепторов при хроническом гепатите С // Клин. лабораторная диагностика. — 2013. — № 2. — С. 23–29. Sysoev K.A., Chukhlovin A.B., Totolian A.A. Diagnosticheskaya rol` opredeleniya khemokinov i ikh retseptorov pri khronicheskom gepatite S [The diagnostic role of chemokines and their receptors in chronic hepatitis C]. Klinicheskaya laboratornaya diagnostika — Clinical Laboratory Diagnostics, 2013, vol. 2, pp. 23–29.
5. Сысоев К.А., Чухловин А.Б., Шахманов Д.М., Жданов К.В., Тотолян А.А. Профиль цитокинов и хемокинов в плазме крови пациентов с хроническим гепатитом С // Инфекция и иммунитет. — 2013. — Т. 3, № 1. — С. 49–58. Sysoev K.A., Chukhlovin A.B., Shakhmanov D.M., Zhdanov K.V., Totolian A.A. Profil` tsitokinov i khemokinov v plazme krovi patsientov s khronicheskim gepatitom S [Cytokines and chemokines in the blood plasma of patients with chronic hepatitis C]. Infektsiya i immunitet — Infection and Immunity, 2013, vol. 3, no. 1, pp. 49–58.
6. Хайдуков С.В., Байдун Л.А., Зурочка А.В., Тотолян А.А. Стандартизованная технология «Исследование субпопуляционного состава лимфоцитов периферической крови с применением проточных цитофлюориметров-анализаторов» (Проект) // Медицинская иммунология. — 2012. — Т. 14, № 3. — С. 255–268. Khaidukov S.V., Baydun L.A., Zurochka A.V., Totolian A.A. Standartizovannaya tekhnologiya “Issledovanie subpopulyatsionnogo sostava limfotsitov perifericheskoy krovi s primeneniem protochnykh tsitoflyuorimetrov-analizatorov” (Proekt) [Standard technology “Flow cytometric immunophenotyping of peripheral blood lymphocytes” (Draft version)]. Meditsinskaya immunologiya — Medical Immunology, 2012, vol. 12, no. 3, pp. 255–268.
7. Annunziato F., Cosmi L., Liotta F., Maggi E., Romagnani S. The phenotype of human Th17 cells and their precursors, the cytokines that mediate their differentiation and the role of Th17 cells in inflammation. Int. Immunol., 2008, vol. 20, pp. 1361–1368.
8. Bromley S., Mempel T., Luster A. Orchestrating the orchestrators: chemokines in control of T cell traffic. Nat. Immunol., 2008, vol. 9, pp. 970–980.
9. Butera D., Marukian S., Iwamaye A., Hembrador E., Chambers T., Di Bisceqlie A., Charles E., Tatal A., Jacobson I., Rice C., Dustin L. Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis C. Blood, 2005, vol. 106, pp. 1175–1182.
10. Casrouge A., Decalf J., Ahloulay M., Lababidi C., Mansour G., Vallet-Pichard A., Mallet V., Mottez E., Mapes J., Fontanet A., Pol S., Albert M. Evidence for an antagonist form of the chemokine CXCL10 in patients chronically infected with HCV. J. Clin. Invest., 2011, vol. 121, pp. 308–317.
11. Crome S., Clive B., Wang A, Kang C, Chow V., Yu J., Lai A., Ghahary A., Broady R., Levings M. Inflammation effects of ex vivo human Th17 cells are suppressed by regulatory T cells. J. Immunol., 2010, vol. 185, pp. 3199–3208.
12. Diago M., Castellano G., Garcia-Samaniego J., Perez C., Fernandez I., Romero M., Iacono O., Garcia-Monson C. Association of pretreatment serum interferon gamma inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis C. Gut, 2006, vol. 55, pp. 374–379.
13. Gonzales V., Falconer K., Blom K., Reichard O., Morn B., Laursen A., Weis N., Alaeus A., Sandberq J. High levels of chronic activation in the T-cell compartments of patients coinfected with hepatitis C virus type 1 and on highly active antiretroviral therapy are reverted by alpha interferon and ribavirin treatment. J. Virol., 2009, vol. 83, pp. 11407–11411.
14. Groom J., Luster A. CXCR3 in T cell function. Exp. Cell Res., 2011, vol. 317, pp. 620–631.
15. Lauer G., Walker B. Hepatitis C virus infection. N. Engl. J. Med., 2001, vol. 345, pp. 41–52.
16. Maecker H., McCoy P., Nussenblatt R. Standardizing immunophenotyping for the human immunology project. Nat. Rev. Immunol., 2012, vol. 12, pp. 191–200.
17. Oo Y., Banz V., Kavanagh D., Liaskou E., Withers D., Humphreys E., Reynolds G., Lee-Turner L., Kalia N., Hubscher S., Klenerman P., Eksteen B., Adams D. CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver. J. Hepatol., 2012, vol. 57, pp. 1044–1051.
18. Oo Y., Shetty S., Adams D. The role of chemokines in the recruitment of lymphocytes to the liver. Dig. Dis., 2010, vol. 28, pp. 31–44.
19. Zeremski M., Petrovic L., Talal A. The role of chemokines as inflammatory mediators in chronic hepatitis C virus infection. J. Viral Hepat., 2007, vol. 14, pp. 675–687.
Russian Journal of Infection and Immunity. 2013; 3: 327-334
ANALYSIS OF T-HELPER SUBSETS OF PERIPHERAL BLOOD OF PATIENTS WITH CHRONIC HEPATITIS C EXPRESSING CHEMOKINE RECEPTORS CXCR3 AND CCR6 AND ACTIVATION MARKERS CD38 AND HLA-DR
https://doi.org/10.15789/2220-7619-2013-4-327-334Abstract
Abstract. In case of hepatitis C the adequate adaptive immune response depends on T-helper lymphocyte subsets and recruiting specific T cells in the site of infection. The purpose of the study was to assess changes in subpopulations of T-helper cells bearing chemokine receptor CXCR3 and CCR6 and activation markers CD38 and HLA-DR in peripheral blood of patients with chronic hepatitis C (n = 19) and healthy donors (n = 32). The T-helper phenotype was assessed by flow cytometry using a combination of monoclonal antibodies HLA-DR-FITC/CD38-PE/CD3-ECD/CCR6-PE-Cy7/CXCR3-APC/CD4-APC-Cy7. It was demonstrated reduction of CD38+ subset, increase of CXCR3+ and CCR6+ subsets of T-helper cells in particular CD3+CD4+ CXCR3+CCR6+ cells and importance of joint determination of the chemokine receptors CXCR3 and CCR6 and the activation markers CD38 and HLA-DR compared to their separate analysis in chronic hepatitis C.
References
1. Arsent'eva N.A., Semenov A.V., Totolyan A.A. Rol' polimorfizma genov tsitokinov pri virusnom gepatite S // Infektsiya i immunitet. — 2012. — T. 2, № 4. — S. 687–698. Arsent`eva N.A., Semenov A.V., Totolian A.A. Rol` polimorfizma genov tsitokinov pri virusnom gepatite S [The role of cytokine gene polymorphism in hepatitis C virus infection]. Infektsiya i immunitet — Infection and Immunity, 2012, vol. 2, no. 4, pp. 687–698.
2. Virusnye gepatity v Rossiiskoi Federatsii. Analiticheskii obzor. 8 vypusk / Pod red. V.I. Pokrovskogo, A.B. Zhebruna. — SPb.: FBUN NIIEM imeni Pastera, 2011. — 116 s. Virusnye gepatity v Rossiyskoy Federatsii. Analiticheskiy obzor. 8 vypusk (Pod red. V.I. Pokrovskogo, A.B. Zhebruna) [Viral hepatitis in Russian Federation. Analytical review. Issue 8 (Ed. Pokrovskiy V.I., Zhebrun A.B.)]. St. Petersburg Pasteur Institute, 2011. 116 p.
3. Zhdanov K.V., Gusev D.A., Chirskii B.C., Sysoev K.A., Yakubovskaya L.A., Shakhmanov D.M., Totolyan A.A. Khronicheskaya HCV-infektsiya i ekspressiya mRNK SS-khemokinov i ikh retseptorov // Zhurnal mikrobiologii, epidemiologii i immunobiologii. — 2008. — № 4. — S. 73–78. Zhdanov K.V., Gusev D.A., Chirskiy B.C., Sysoev K.A., Yakubovskaya L.A., Shakhmanov D.M., Totolian A.A. Hronicheskaya HCV-infektsiya i ekspressiya mRNK SS-khemokinov i ikh retseptorov [Chronic HCV infection and mRNA expression of CC-chemokines and their receptors]. Zhurnal mikrobiologii, epidemiologii i immunobiologii — Journal of Microbiology, Epidemiology and Immunobiology, 2008, vol. 4, pp. 73–78.
4. Sysoev K.A., Chukhlovin A.B., Totolyan A.A. Diagnosticheskaya rol' opredeleniya khemokinov i ikh retseptorov pri khronicheskom gepatite S // Klin. laboratornaya diagnostika. — 2013. — № 2. — S. 23–29. Sysoev K.A., Chukhlovin A.B., Totolian A.A. Diagnosticheskaya rol` opredeleniya khemokinov i ikh retseptorov pri khronicheskom gepatite S [The diagnostic role of chemokines and their receptors in chronic hepatitis C]. Klinicheskaya laboratornaya diagnostika — Clinical Laboratory Diagnostics, 2013, vol. 2, pp. 23–29.
5. Sysoev K.A., Chukhlovin A.B., Shakhmanov D.M., Zhdanov K.V., Totolyan A.A. Profil' tsitokinov i khemokinov v plazme krovi patsientov s khronicheskim gepatitom S // Infektsiya i immunitet. — 2013. — T. 3, № 1. — S. 49–58. Sysoev K.A., Chukhlovin A.B., Shakhmanov D.M., Zhdanov K.V., Totolian A.A. Profil` tsitokinov i khemokinov v plazme krovi patsientov s khronicheskim gepatitom S [Cytokines and chemokines in the blood plasma of patients with chronic hepatitis C]. Infektsiya i immunitet — Infection and Immunity, 2013, vol. 3, no. 1, pp. 49–58.
6. Khaidukov S.V., Baidun L.A., Zurochka A.V., Totolyan A.A. Standartizovannaya tekhnologiya «Issledovanie subpopulyatsionnogo sostava limfotsitov perifericheskoi krovi s primeneniem protochnykh tsitoflyuorimetrov-analizatorov» (Proekt) // Meditsinskaya immunologiya. — 2012. — T. 14, № 3. — S. 255–268. Khaidukov S.V., Baydun L.A., Zurochka A.V., Totolian A.A. Standartizovannaya tekhnologiya “Issledovanie subpopulyatsionnogo sostava limfotsitov perifericheskoy krovi s primeneniem protochnykh tsitoflyuorimetrov-analizatorov” (Proekt) [Standard technology “Flow cytometric immunophenotyping of peripheral blood lymphocytes” (Draft version)]. Meditsinskaya immunologiya — Medical Immunology, 2012, vol. 12, no. 3, pp. 255–268.
7. Annunziato F., Cosmi L., Liotta F., Maggi E., Romagnani S. The phenotype of human Th17 cells and their precursors, the cytokines that mediate their differentiation and the role of Th17 cells in inflammation. Int. Immunol., 2008, vol. 20, pp. 1361–1368.
8. Bromley S., Mempel T., Luster A. Orchestrating the orchestrators: chemokines in control of T cell traffic. Nat. Immunol., 2008, vol. 9, pp. 970–980.
9. Butera D., Marukian S., Iwamaye A., Hembrador E., Chambers T., Di Bisceqlie A., Charles E., Tatal A., Jacobson I., Rice C., Dustin L. Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis C. Blood, 2005, vol. 106, pp. 1175–1182.
10. Casrouge A., Decalf J., Ahloulay M., Lababidi C., Mansour G., Vallet-Pichard A., Mallet V., Mottez E., Mapes J., Fontanet A., Pol S., Albert M. Evidence for an antagonist form of the chemokine CXCL10 in patients chronically infected with HCV. J. Clin. Invest., 2011, vol. 121, pp. 308–317.
11. Crome S., Clive B., Wang A, Kang C, Chow V., Yu J., Lai A., Ghahary A., Broady R., Levings M. Inflammation effects of ex vivo human Th17 cells are suppressed by regulatory T cells. J. Immunol., 2010, vol. 185, pp. 3199–3208.
12. Diago M., Castellano G., Garcia-Samaniego J., Perez C., Fernandez I., Romero M., Iacono O., Garcia-Monson C. Association of pretreatment serum interferon gamma inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis C. Gut, 2006, vol. 55, pp. 374–379.
13. Gonzales V., Falconer K., Blom K., Reichard O., Morn B., Laursen A., Weis N., Alaeus A., Sandberq J. High levels of chronic activation in the T-cell compartments of patients coinfected with hepatitis C virus type 1 and on highly active antiretroviral therapy are reverted by alpha interferon and ribavirin treatment. J. Virol., 2009, vol. 83, pp. 11407–11411.
14. Groom J., Luster A. CXCR3 in T cell function. Exp. Cell Res., 2011, vol. 317, pp. 620–631.
15. Lauer G., Walker B. Hepatitis C virus infection. N. Engl. J. Med., 2001, vol. 345, pp. 41–52.
16. Maecker H., McCoy P., Nussenblatt R. Standardizing immunophenotyping for the human immunology project. Nat. Rev. Immunol., 2012, vol. 12, pp. 191–200.
17. Oo Y., Banz V., Kavanagh D., Liaskou E., Withers D., Humphreys E., Reynolds G., Lee-Turner L., Kalia N., Hubscher S., Klenerman P., Eksteen B., Adams D. CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver. J. Hepatol., 2012, vol. 57, pp. 1044–1051.
18. Oo Y., Shetty S., Adams D. The role of chemokines in the recruitment of lymphocytes to the liver. Dig. Dis., 2010, vol. 28, pp. 31–44.
19. Zeremski M., Petrovic L., Talal A. The role of chemokines as inflammatory mediators in chronic hepatitis C virus infection. J. Viral Hepat., 2007, vol. 14, pp. 675–687.
