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Медицинская иммунология

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МАЛЫЕ СУБПОПУЛЯЦИИ Т-ХЕЛПЕРОВ (Th НАИВНЫЕ ТИМИЧЕСКИЕ, Th НАИВНЫЕ ЦЕНТРАЛЬНЫЕ, Th9, Th22 И CD4+CD8+ ДВАЖДЫ ПОЛОЖИТЕЛЬНЫЕ Т-КЛЕТКИ)

https://doi.org/10.15789/1563-0625-2013-6-503-512

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Аннотация

Резюме. Одну из ключевых ролей в процессах, происходящих в организме при попадании чужеродного антигена, играют Т-клетки, а именно Т-хелперы (Th). Появление новых высокочувствительных инструментов позволило исследовать более тонкую структурную организацию Т-клеток, выявить среди них целый ряд функционально значимых малых субпопуляций. Данные Т-клетки были охарактеризованы как фенотипически, так и функционально. Представленный обзор посвящен Th наивным тимическим, Th наивным центральным, Th9, Th22 и CD4+CD8+ дважды положительным Т-клеткам, отражена их роль и функциональная значимость при различных патологических состояниях. В настоящее время имеются четкие данные о наличии определенных наборов мембранных молекул, транскрипционных факторов и продукции специфических медиаторов иммунной системы, отличающих эти субпопуляции.

Использование этих данных в лабораторных исследованиях, несомненно, скажется на качестве диагностики нарушений функционирования иммунной системы и адекватности назначаемой иммунотерапии.

Об авторе

С. В. Хайдуков
ФГБУ «Федеральный научно-клинический центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава РФ, Москва; Технопарк, ФГБУН «Институт биоорганической химии имени академиков М.М. Шемякина и Ю.А. Овчинникова» РАН, Москва
Россия

д.б.н., заведующий лабораторией клеточной иммунологии, старший научный сотрудник 

117997, ГСП-7, ул. Миклухо-Маклая, 16/10. Тел.: 8 (985) 923-41-62



Список литературы

1. Хайдуков С.В., Зурочка А.В. Цитометрический анализ субпопуляций Т-хелперов (Th1, Th2, Treg, Th17, Т-хелперы активированные) // Медицинская иммунология. – 2011. – Т. 13, № 1. – С. 7-16. Khaidukov S.V., Zurochka A.V. Tsitometricheskiy analiz subpopulyatsiy T-khelperov (Th1, Th2, Treg, Th17, T-khelpery aktivirovannye) [Analysis of T helper subpopulations (Th1, Th2, Treg, Th17, activated T-helpers) by means of flow cytometry]. Meditsinskaya immunologiya – Medical Immunology, 2011, vol. 13, no. 1, pp. 7-16.

2. Хайдуков С.В., Зурочка А.В., Черешнев В.А. Цитометрический анализ в клинической иммунологии. – Екатеринбург: УрО РАН. – 2011. – 221 c. Khaidukov S.V., Zurochka A.V., Chereshnev V.A. Tsitometricheskiy analiz v klinicheskoy immunologii [Cytometric analysis for clinical immunology]. Ekaterinburg, Ural Branch of the Russian Academy of Sciences, 2011. 221 p.

3. Annunziato F., Romagnani S. Heterogeneity of human effector CD4+ T cells. Arthritis. Res. Ther., 2009, vol. 11, no. 6, p. 257.

4. Bang K., Lund M., Wu. K., Mogensen S.C., Thestrup-Pedersen K. CD4+CD8+ (thymocyte-like) T lymphocytes present in blood and skin from patients with atopic dermatitis suggest immune dysregulation. Br. J. Dermatol., 2001, vol. 144, pp. 1140-1147.

5. Berrih S., Gaud C., Bach M.A., Le Brigand H., Binet J.P., Bach J.F.. Evaluation of T cell subsets in myasthenia gravis using anti-T cell monoclonal antibodies. Clin. Exp. Immunol., 1981, vol. 45, pp. 1-8.

6. Bird I.N., Spragg J.H., Ager A., Matthews N. Studies of lymphocyte transendothelial migration: analysis of migrated cell phenotypes with regard to CD31 (PECAM-1), CD45RA and CD45R0. Immunology, 1993, vol. 80, pp. 553-560.

7. Blue M.L., Daley J.F., Levine H., Schlossman S.F. Coexpression of T4 and T8 on peripheral blood T cells demonstrated by two-color fluorescence flow cytometry. J. Immunol., 1985, vol. 134, pp. 2281-2286.

8. Bofill M., Martinez-Picado J., Ruiz-Hernandez R., Cabrera C., Marfil S., Erkizia I., Bellido R., Romeu J., Clotet B., Ruiz L. Naive CD4(+) T cells and recent thymic emigrant levels in treated individuals with HIV: clinical relevance. AIDS. Res. Hum. Retroviruses, 2006, vol. 22, pp. 893-896.

9. Bonomo A., Kehn P.J., Shevach E.M. Premature escape of double-positive thymocytes to the periphery of young mice: possible role in autoimmunity. J. Immunol., 1994, vol. 152, pp. 1509-1514.

10. Brenchley J.M., Hill B.J., Ambrozak D.R., Price D.A., Guenaga F.J., Casazza J.P., Kuruppu J., Yazdani J., Migueles S.A., Connors M., Roederer M., Douek D.C., Koup R.A. T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis. J. Virol., 2004, vol. 78, pp. 1160-1168.

11. Chang H., Hanawa H., Liu H., Yoshida T., Hayashi M., Watanabe R., Abe S., Toba K., Yoshida K., Elnaggar R., Minagawa S., Okura Y., Kato K., Kodama M., Maruyama H., Miyazaki J., Aizawa Y. Hydrodynamicbased delivery of an interleukin-22-Ig fusion gene ameliorates experimental autoimmune myocarditis in rats. J. Immunol., 2006, vol. 177, no. 6, pp. 3635-3643.

12. Chang H.C., Sehra S., Goswami R., Yao W., Yu Q., Stritesky G.L., Jabeen R., McKinley C., Ahyi A.N., Han L., Nguyen E.T., Robertson M.J., Perumal N.B., Tepper R.S., Nutt S.L., Kaplan M.H. The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nat. Immunol., 2010, vol. 11, pp. 527-534.

13. Dardalhon V., Awasthi A., Kwon H., Galileos G., Gao W., Sobel R.A., Mitsdoerffer M., Strom T.B., Elyaman W., Ho I.C., Khoury S., Oukka M., Kuchroo V.K. IL-4 inhibits TGF-β-induced Foxp3+ T cells and, together with TGF-β, generates IL-9+IL-10+Foxp3- effector T cells. Nat. Immunol., 2008, vol. 9, pp. 1347-1355.

14. De Rosa S.C., Herzenberg L.A., Herzenberg L.A., Roederer M. 11-color, 13-parameter flow cytometry: identification of human naive T cells by phenotype, function, and T-cell receptor diversity. Nat. Med., 2001, vol. 7, pp. 245-248.

15. Demeure C.E., Byun D.G., Yang L.P., Vezzio N., Delespesse G. CD31 (PECAM-1) is a differentiation antigen lost during human CD4 T-cell maturation into Th1 or Th2 effector cells. Immunology, 1996, vol. 88, pp. 110-115.

16. Douek D.C., McFarland R.D., Keiser P.H., Gage E.A., Massey J.M., Haynes B.F., Polis M.A., Haase A.T., Feinberg M.B., Sullivan J.L., Jamieson B.D., Zack J.A., Picker L.J., Koup R.A. Changes in thymic function with age and during the treatment of HIV infection. Nature, 1998, vol. 396, pp. 690-695.

17. Duhen T., Geiger R., Jarrossay D., Lanzavecchia A., Sallusto F. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nature. Immunology, 2009, vol. 10, no. 8, pp. 857-863.

18. Duszczyszyn D.A., Beck J.D., Antel J., Bar-Or A., Lapierre Y., Gadag V., Haegert D.G. Altered naive CD4 and CD8 T cell homeostasis in patients with relapsing-remitting multiple sclerosis: thymic versus peripheral (nonthymic) mechanisms. Clin. Exp. Immunol., 2006, vol. 143, pp. 305-313.

19. Eyerich S., Eyerich K., Pennino D., Carbone T., Nasorri F., Pallotta S., Cianfarani F., Odorisio T., Traidl-Hoffmann C., Behrendt H., Durham S.R., Schmidt-Weber C.B., Cavani A. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J. Clin. Invest., 2009, vol. 119, no. 12, pp. 3573-3585.

20. Hauber H.P., Bergeron C., Hamid Q. IL-9 in allergic inflammation. Int. Arch. Allergy. Immunol., 2004, vol. 134, pp. 79-87.

21. Isgro A., Marziali M., Mezzaroma I., Luzi G., Mazzone A.M., Guazzi V., Andolfi G., Cassani B., Aiuti A., Aiuti F. Bone marrow clonogenic capability, cytokine production, and thymic output in patients with common variable immunodeficiency. J. Immunol., 2005, vol. 174, pp. 5074-5081.

22. Iwatani Y., Hidaka Y., Matsuzuka F., Kuma K., Amino N. Intrathyroidal lymphocyte subsets, including unusual CD4+CD8+ cells and CD3loTCR alpha-beta loy-CD4-CD8- cells, in autoimmune thyroid disease. Clin. Exp. Immunol., 1993, vol. 93, pp. 430-436.

23. Jimenez E., Sacedon R., Vicente A., Hernandez-Lopez C., Zapata A.G., Varas A. Rat peripheral CD4+CD8+ T lymphocytes are partially immunocompetent thymus-derived cells that undergo post-thymic maturation to become functionally mature CD4+ T lymphocytes. J. Immunol., 2002, vol. 168, pp. 5005-5013.

24. Junge S., Kloeckener-Gruissem B., Zufferey R., Keisker A., Salgo B., Fauchere J.C., Scherer F., Shalaby T., Grotzer M., Siler U., Seger R., G ng r T. Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children. Eur. J. Immunol., 2007, vol. 37, pp. 3270-3280.

25. Kilpatrick R.D., Rickabaugh T., Hultin L.E., Hultin P., Hausner M.A., Detels R., Phair J., Jamieson B.D. Homeostasis of the naive CD4+ T cell compartment during aging. J. Immunol., 2008, vol. 180, pp. 1499-1507.

26. Kimmig S., Przybylski G.K., Schmidt C.A., Laurisch K., M wes B., Radbruch A., Thiel A. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J. Exp. Med., 2002, vol. 195, pp. 789-794.

27. Koetz K., Bryl E., Spickschen K., O’Fallon W.M., Goronzy J.J., Weyand C.M. T cell homeostasis in patients with rheumatoid arthritis. Proc. Natl. Acad. Sci. USA, 2000, vol. 97, pp. 9203-9208.

28. Kohler S., Thiel A. Life after the thymus: CD31+ and CD31- human naive CD4+ T-cell subsets. Blood, 2009, vol. 113, pp. 769-774.

29. Kohler S., Wagner U., Pierer M., Kimmig S., Oppmann B., M wes B., J lke K., Romagnani C., Thiel A. Post-thymic in vivo proliferation of naive CD4+ T cells constrains the TCR repertoire in healthy human adults. Eur. J. Immunol., 2005, vol. 35, pp. 1987-1994.

30. Li H., Rostami A. IL-9: basic biology, signaling pathways in CD4+ T cells and implications for autoimmunity. J. Neuroimmune. Pharmacol., 2010, vol. 5, pp. 198-209.

31. Muller, W.A., Weigl S.A., Deng X., Phillips D.M. PECAM-1 is required for transendothelial migration of leukocytes. J. Exp. Med., 1993, vol. 178, pp. 449-460.

32. Muraro P.A., Douek D.C., Packer A., Chung K., Guenaga F.J, Cassiani-Ingoni R., Campbell C., Memon S., Nagle J.W., Hakim F.T., Gress R.E., McFarland H.F., Burt R.K., Martin R. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J. Exp. Med., 2005, vol. 201, pp. 805-816.

33. Nascimbeni M., Shin E.C., Chiriboga L., Kleiner D.E., Rehermann B. Peripheral CD4(+)CD8(+) T cells are differentiated effector memory cells with antiviral functions. Blood, 2004, vol. 104, pp. 478-486.

34. Newman P.J. Switched at birth: a new family for PECAM-1. J. Clin. Invest., 1999, vol. 103, pp. 5-9.

35. Newman P.J., Berndt M.C., Gorski J., White II G.C., Lyman S., Paddock C., Muller W.A. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science, 1990, vol. 247, pp. 1219-1222.

36. Nickel P., Kreutzer S., Bold G., Friebe A., Schmolke K., Meisel C., Jurgensen J.S., Thiel A., Wernecke K.D., Reinke P., Volk H.D. CD31+ naїve Th cells are stable during six months following kidney transplantation: implications for posttransplant thymic function. Am. J. Transplant., 2005, vol. 5, pp. 1764-1771.

37. Nobile M., Correa R., Borghans J.A., D’Agostino C., Schneider P., De Boer R.J., Pantaleo G. De novo T-cell generation in patients at different ages and stages of HIV-1 disease. Blood, 2004, vol. 104, pp. 470-477.

38. Nowak E.C., Weaver C.T., Turner H., Begum-Haque S., Becher B., Schreiner B., Coyle A.J., Kasper L.H., Noelle R.J. IL-9 as a mediator of Th17-driven inflammatory disease. J. Exp. Med., 2009, vol. 206, pp. 1653-1660.

39. Ober B.T., Summerfield A., Mattlinger C., Wiesm ller K.H., Jung G., Pfaff E., Saalm ller A., Rziha H.J. Vaccine-induced, pseudorabies virus-specific, extrathymic CD4+CD8+ memory T-helper cells in swine. J. Virol., 1998, vol. 72, pp. 4866-4873.

40. Ortolani C., Forti E., Radin E., Cibin R., Cossarizza A. Cytofluorimetric identification of two populations of double positive (CD4+, CD8+) T lymphocytes in human peripheral blood. Biochem. Biophys. Res. Commun., 1993, vol. 191, pp. 601-609.

41. Pahar B., Lackner A.A., Veazey R.S. Intestinal double-positive CD4+CD8+ T cells are highly activated memory cells with an increased capacity to produce cytokines. Eur. J. Immunol., 2006, vol. 36, pp. 583-592.

42. Parel Y., Aurrand-Lions M., Scheja A., Dayer J.M., Roosnek E., Chizzolini C. Presence of CD4+CD8+ double-positive T cells with very high interleukin-4 production potential in lesional skin of patients with systemic sclerosis. Arthritis. Rheum., 2007, vol. 56, pp. 3459-3467.

43. Periwal S.B., Cebra J.J. Respiratory mucosal immunization with reovirus serotype 1/L stimulates virusspecific humoral and cellular immune responses, including double-positive (CD4(+)/ CD8(+)) T cells. J. Virol., 1999, vol. 73, pp. 7633-7640.

44. Ponchel F., Morgan A.W., Bingham S.J., Quinn M., Buch M., Verburg R.J., Henwood J., Douglas S.H., Masurel A., Conaghan P., Gesinde M., Taylor J., Markham A.F., Emery P., van Laar J.M., Isaacs J.D. Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis. Blood, 2002, vol. 100, pp. 4550-4556.

45. Sala P., Tonutti E., Feruglio C., Florian F., Colombatti A. Persistent expansions of CD4+CD8+ peripherals blood T cells. Blood, 1993, vol. 82, pp. 1546-1552.

46. Schmid J.M., Junge S.A., Hossle J.P., Schneider E.M., Roosnek E., Seger R.A., Gungor T. Transient hemophagocytosis with deficient cellular cytotoxicity, monoclonal immunoglobulin M gammopathy, increased T-cell numbers, and hypomorphic NEMO mutation. Pediatrics, 2006, vol. 117, pp. e1049-e1056.

47. Song K., Rabin R.L., Hill B.J., De Rosa S.C., Perfetto S.P., Zhang H.H., Foley J.F., Reiner J.S., Liu J., Mattapallil J.J., Douek D.C., Roederer M., Farber J.M. Characterization of subsets of CD4+ memory T cells reveals early branched pathways of T cell differentiation in humans. Proc. Natl. Acad. Sci. USA, 2005, vol. 102, pp. 7916-7921.

48. Soroosh P., Doherty T.A. Th9 and allergic disease. Immunology, 2009, vol. 127, no. 4, pp. 450-458.

49. Stockinger H., Schreiber W., Majdic O., Holter W., Maurer D., Knapp W. Phenotype of human T cells expressing CD31, a molecule of the immunoglobulin supergene family. Immunology, 1992, vol. 75, pp. 53-58.

50. Tada Y., Koarada S., Morito F., Ushiyama O., Haruta Y., Kanegae F., Ohta A., Ho A., Mak T.W., Nagasawa K. Acceleration of the onset of collageninduced arthritis by a deficiency of platelet endothelial cell adhesion molecule 1. Arthritis. Rheum., 2003, vol. 48, pp. 3280-3290.

51. Thiel A., Alexander T., Schmidt C.A., Przybylski G.K., Kimmig S., Kohler S., Radtke H., Gromnica-Ihle E., Massenkeil G., Radbruch A., Arnold R., Hiepe F. Direct assessment of thymic reactivation after autologous stem cell transplantation. Acta. Haematol., 2008, vol. 119, pp. 22-27.

52. Thiel A., Schmitz J., Miltenyi S., Radbruch A. CD45RA-expressing memory/effector Th cells committed to production of interferon-gamma lack expression of CD31. Immunol. Lett., 1997, vol. 57, pp. 189-192.

53. Van Snick J., Goethals A., Renauld J.C., Van Roost E., Uyttenhove C. Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40). J. Exp. Med., 1989, vol. 169, pp. 363-368.

54. Veldhoen M., Uyttenhove C., van Snick J., Helmby H., Westendorf A., Buer J., Martin B., Wilhelm C., Stockinger B. Transforming growth factor-beta ‘reprograms’ the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat. Immunol., 2008, vol. 9, pp. 1341-1346.

55. Weiss L., Roux A., Garcia S. Persistent expansion, in a human immunodeficiency virus-infected person, of V beta-restricted CD4+CD8+ T lymphocytes that express cytotoxicity-associated molecules and are committed to produce interferon-gamma and tumor necrosis factor-alpha. J. Infect. Dis., 1998, vol. 178, pp. 1158-1162.

56. Wolk K. Sabat R. Interleukin-22: a novel T- and NK-cell derived cytokine that regulates the biology of tissue cells. Cytokine. Growth. Factor. Rev., 2006, vol. 17, pp. 367-380.

57. Wolk K., Witte E., Wallace E., Docke W.D., Kunz S., Asadullah K., Volk H.D., Sterry W., Sabat R. IL- 22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur. J. Immunol., 2006, vol. 36, no. 5, pp. 1309-1323.

58. Ye Z.J., Yuan M.L., Zhou Q., Du R.H., Yang W.B., Xiong X.Z., Zhang J.C., Wu C., Qin S.M., Shi H.Z. Differentiation and recruitment of Th9 cells stimulated by pleural mesothelial cells in human Mycobacterium tuberculosis infection. PloS One, 2012, vol. 7, no. 2, p. e31710.

59. Zenewicz L.A., Yancopoulos G.D., Valenzuela D.M., Murphy A.J., Karow M., Flavell R.A. Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity, 2007, vol. 27, no. 4, pp. 647-659.

60. Zhang N., Pan H.F., Ye D.Q. Th22 in inflammatory and autoimmune disease: prospects for therapeutic intervention. Mol. Cell. Biochem., 2011, vol. 353, pp. 41-46.

61. Zuckermann F.A. Extrathymic CD4/CD8 double positive T cells. Veterinary. Immunol. Immunopathol., 1999, vol. 72, pp. 55-66.

62. Zuckermann F.A., Husmann R.J. Functional and phenotypic analysis of porcine peripheral blood CD4/CD8 double-positive T cells. Immunology, 1996, vol. 87, pp. 500-512.


Для цитирования:


Хайдуков С.В. МАЛЫЕ СУБПОПУЛЯЦИИ Т-ХЕЛПЕРОВ (Th НАИВНЫЕ ТИМИЧЕСКИЕ, Th НАИВНЫЕ ЦЕНТРАЛЬНЫЕ, Th9, Th22 И CD4+CD8+ ДВАЖДЫ ПОЛОЖИТЕЛЬНЫЕ Т-КЛЕТКИ). Медицинская иммунология. 2013;15(6):503-512. https://doi.org/10.15789/1563-0625-2013-6-503-512

For citation:


Khaidukov S.V. MINOR SUBSETS OF T-HELPER CELLS (Th THYMIC NAIVE, Th CENTRAL NAIVE, Th9, Th22 AND CD4+CD8+ DOUBLE POSITIVE T-CELLS). Medical Immunology (Russia). 2013;15(6):503-512. (In Russ.) https://doi.org/10.15789/1563-0625-2013-6-503-512

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