Russian Pediatric OphthalmologyRussian Pediatric OphthalmologyРоссийская педиатрическая офтальмология1993-18592412-432XEco-Vector3960510.18821/1993-1859-2018-13-1-46-53ArticlesСтатьиReview ArticleINVESTIGATION OF T-REGULATORY CELLS IN PREMATURY INFANTSИССЛЕДОВАНИЕ Т-РЕГУЛЯТОРНЫХ КЛЕТОК У НЕДОНОШЕННЫХ ДЕТЕЙKuznetsovaYulia DmytriеvnaКузнецоваЮлия Дмитриевна

«RAMS “Russian children’s Clinical Hospital” of Ministry of health of Russian Federation, doctor of oftolmology department, The Highest category doctor, Moscow, 117997

врач-офтальмолог отделения офтальмологии ФГБУ РДКБ Минздрава РФ, 117997, Москва

kuznecovay@mail.ruBalashovaL. MБалашоваЛ. МBykovskayaS. NБыковскаяС. НRussian children’s Clinical Hospital Russian Ministry of healthФГБУ «Российская детская клиническая больница» Минздрава РоссииN.I. Pyrogov Russian national research Medical University Ministry of healthГБОУ ВПО «Российский национальный исследовательский медицинский Университет им. Н.И. Пирогова»15032018131VOL 13, NO1 (2018)ТОМ 13, №1 (2018)465322072020Copyright ©; 2018, Eco-VectorCopyright ©; 2018, ООО "Эко-Вектор"2018Eco-VectorООО "Эко-Вектор"https://ruspoj.com/1993-1859/article/view/39605

Violation of the regulation of congenital immune reactions plays an important role in the etiology of common and serious neonatal complications in prematurely born children such as bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity and others. This review is devoted to the study of one of the indicators of cellular immunity - T-regulatory cells CD4 + CD25 + FoxP3 + CD127low in prematury infants. Further studies of immunity and in particular T-regulatory cells in premature infants in various diseases, including retinopathy of prematurity, will further develop pathogenetically substantiated correction of immunological disorders to prevent their occurrence and progression.

Нарушение регуляции врожденных иммунных реакций играет важную роль в этиологии распространенных и серьезных неонатальных осложнений у преждевременно рожденных детей, таких как бронхолегочная дисплазия, некротический энтероколит, ретинопатия недоношенных и другие. Данный обзор посвящен исследованию одного из показателей клеточного иммунитета Т-регуляторных клеток CD4+CD25+FoxP3+CD127low у недоношенных детей. Дальнейшие исследования иммунитета, и в частности Т-регуляторных клеток у недоношенных детей при различных заболеваниях, в том числе при ретинопатии недоношенных, позволят разработать патогенетически обоснованную коррекцию иммунологических нарушений для профилактики их возникновения и прогрессирования.

T-regulatory cellsprematury infantsТ-регуляторные клеткинедоношенные детиNanthakumar N., Meng D., Goldstein A.M., Zhu W., Lu L., Uauy R., Llanos A., Claud E.C., Walker W.A. The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: an immature innate immune response. 2011; PLoS One.; 6: e17776.Nathe K.E., Parad R., Van Marter L.J., Lund C.A., Suter E.E., Hernandez-diaz S., Boush E.B., Ikonomu E., Gallington L., Morey J.A., Zeman A.M., McNamara M., Levy O. Endotoxin-directed innate immunity in tracheal aspirates of mechanically ventilated human neonates. Pediatr. Res. 2009; 66: 191-6.Cupedo T., Nagasawa M., Weijer K., Blom B., Spits H. Development and activation of regulatory T cells in the human fetus. Eur. J. Immunol. 2005; 35, 383-90.Ярилин А.А. Иммунология. СПб: Москва, 2010. 334-5.Быковская С.Н., Карасев А.В., Лохонина А.В., Клейменова Е.Б. Анализ Т-регуляторных клеток CD4+CD25+FOXP3+ при аутоиммунных заболеваниях. Молекулярная медицина. 2013; (3): 20-8.Jiang S., Lechler R.I., He X.S., Huang J.F. Regulatory T cells and transplantation tolerance. Hum. Immunol. 2006; 67 (10): 765-76.Xu Y.Q., Gao Y.D., Yang J., Guo W. A defect of CD4+CD25+ reg-ulatory T-cells in inducing interleukin-10 production from CD4+ T-cells under CD46 costimulation in asthma patients. J. Asthma. 2010; 47 (4): 367-73.Dejaco C., Duftner C., Grubeck-Loebenstein B., Schirmer M. Imbalance of regulatory T-cells in human autoimmune diseases. Immunology. 2006; 117 (3): 289-300.Venken K., Hellings N., Thewissen M. et al. Compromised CD4+ CD25high regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level. Immunology. 2008; 123 (1): 79-89.Елисеева Д.Д., Лифшиц Г.В.,Лохонина А.В.,Жданов Д.Д., Завалишин И.А., Быковская С.Н., Лечение выращенными ex vivo аутологичными регуляторными Т-клетками CD4+CD25+FOXP3+CD127LOW восстанавливает баланс иммунной системы пациентов с ремитирующим рассеянным склерозом. Журнал неврологии и психиатрии им. С.С. Корсакова, 2016; 116(2-2): 54-62.Battaglia M., A.Stabilini, and E.Tresoldi.2012. Expanding human T-regulatory cells with the mTOR-inhibitor rapamycin.Meth. Mol. Biol. 821: 279-93.Zheng S.G., J. Wang, P. Wang, et al. 2007. IL-2 is essential for TGF-beta to convert naïve CD4+CD25-cells to CD25+Foxp3+ regulatory T-cells and for expansion of these cells. J. Immunol. 178: 2018-27.Панкратьева Л.Л., Мухин В.Е., Чернова М.А., Милева О.И., Солдатова И.Г., Быковская С.Н., Володин Н.Н. Т-регуляторные CD4+CD25highFoxp3+-лимфоциты периферической крови и их значение в патологии неонатального периода. Вопросы практической педиатрии. 2013; 8 (1): 8-13.Viscardi R.M., et al. Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants. Pediatr. Res. 2004; 55(6):1009-17.Chang B.A., Huang Q., Quan J., Chau V., Ladd M., Kwan E., McFadden D.E., Lacaze-Masmonteil T., Miller S.P., Lavoie P.M. Early inflammation in the absence of overt infection in preterm neonates exposed to intensive care. Cytokine. 2011; 56: 621-6.Vento M., Moro M., Escrig R., Arruza L., Villar G., Izquierdo I., Roberts L.J, Arduini A., Escobar J.J., Sastre J., Asensi M.A. Preterm Resuscitation With Low Oxygen Causes Less Oxidative Stress, Inflammation, and Chronic Lung Disease. Pediatrics. 2009; 124: 439-49.Панкратьева Л.Л., Мухин В.Е., Чернова М.А. Вариабельность размеров вилочковой железы у недоношенных детей различного гестационного возраста с осложненным течением неонатального периода: ультразвуковые и клинико-иммунологические параллели. Иммунопатология и клиническая иммунология. 2014; 35(1): 37-44.Isroilov R.I., Khamdamov R.Kh. Diagnostic algorithms of morphological parameters of the thymus gland in the development of various diseases in premature infants]. Lik. Sprava. 2003 Oct-Nov; (7): 87-90.Jeppesen D.L., Hasselbalch H., Nielsen S.D., Sоrensen T.U., Ersbоll A.K., Valerius N.H., Heilmann C.Thymic size in preterm neonates: a sonographic study. Acta. Paediatr. 2003 Jul; 92(7): 817-22.Correa-Rocha R., Perez A., Lorente R., Ferrando-Martinez S., Leal M., et al. Preterm neonates show marked leukopenia and lymphopenia that are associated with increased regulatory T-cell values and diminished IL-7. Pediatr. Res. 2012; 71: 590-7.Georgeson G.D., Szony B.J., Streitman K., Kovács A., Kovács L., László A. Natural killer cell cytotoxicity is deficient in newborns with sepsis and recurrent infections. Eur. J. Pediatr. 2001; 160: 478-82.Harris J., Hazenberg M., Poulin J., Higuero-Alhina D., Schmidt D., Gotway M. et al. Multiparameter evaluation of human thymic function: interpretation and caveats. Clin. Immunol. 2005; 115 (2): 138-46.Ladi E., Yin X., Robey E. Thymic microenvironments for T cell differentiation and selection. Nature. Immunol. 2006; 7 (4): 338-43.Marchant A., Goldman M. T cell-mediated immune responses in human newborns: ready to learn? Clin. Exp. Immunol. 2005; 141 (1):10-8.De Felice C., Latini G., Del Vecchio A., Toti P., Bagnoli F., Petraglia F. Small thymus at birth: a predictive radiographic sign of bronchopulmonary dysplasia. Pediatrics. 2002 Aug; 110 (2 Pt 1): 386-8.Hale L.P., Braun R.D., Gwinn W.M., Greer P.K., Dewhirst M.W. Hypoxia in the thymus: role of oxygen tension in thymocyte survival. Am. J. Physiol. Heart. Circ. Physiol. 2002; 282: H1467-H77.Bodey B., Bodey B.J., Siegel S.E., Kaiser H.E. Involution of the mammalian thymus, one of the leading regulators of aging. In. Vivo. 1997;11:421-40.Rosen D, Lee J.H, Cuttitta F, Rafiqi F, Degan S, Sunday M.E. Accelerated thymic maturation and autoreactive T cells in bronchopulmonary dysplasia. Am. J. Respir. Crit. Care Med. 2006 Jul 1; 174(1): 75-83.Aluvihare V.R., Kallikourdis M., Betz A.G.: Regulatory T cells mediate maternal tolerance to the fetus. Nat. Immunol. 2004; 5: 266-71.Heikkinen J., Mottonen M,Alanen A., Lassila O. Phenotypic characterization of regulatory T cells in the human decidua. Clin. Exp. Immunol. 2004;136:373-78.Mjösberg J., Berg G,Jenmalm M.C., Ernerudh J.: FOXP3+ regulatory T-cells and T-helper1, T-helper 2, and T-helper 17 cells in human early pregnancy decidua. Biol Reprod. 2010; 82(4): 698-705.Sasaki Y., Miyazaki S., Sakai M., Saito S.: CD4+ CD25+ regulatory T-cells are increased in the human early pregnancy decidua and have immunosuppressive activity. Am. J. Reprod. Immunol. 2003;49: 356-61.Somerset D.A., Zheng Y.,Kilby M.D., Sansom D.M.,Drayson M.T.: Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset. Immunology. 2004;112: 38-43.Tilburgs T., Roelen D.L., van der Mast B.J., van Schip J.J., Kleijburg C., de Groot-Swings G.M., Kanhai H.H.Н., Claas F.H.J., Scherjon S.A: Differential distribution of CD4+ CD25bright and CD8+ CD28- T-cells in decidua and maternal blood during pregnancy. Placenta. 2006; 27: 47-53.Dimova T., Nagaeva O., Stenqvist A.C., Hedlund M., Kjellberg L., Strand M., Dehlin E., Mincheva-Nilsson L.Maternal Foxp3 expressing CD4+ CD25+ and CD4+ CD25- regulatory T-cell populations are enriched in humanearly normal pregnancy decidua: a phenotypic study of paired decidual and peripheral blood samples. Am. J. Reprod. Immunol. 2011, Jul; 66 Suppl. 1: 44-56.Winger E.E., Reed J.: Low circulating CD4+ CD25+ FoxP3+ T-regulatory cell levels predict misscarriage risk in newly pregnant women with a history of failure. Am. J. Reprod. Immunol. 2011; 65.Luciano A.A., Arbona-Ramirez I.M., Ruiz R., Llorens-Bonilla B.J., Martinez-Lopez D.G., Funderburg N., Dorsey M.J., Alteration in Regulatory T-cell Subpopulation seen in preterm infants. 2014: PLoS One 6: e95867.Rueda Cesar M., Wells Casey B., Gisslen Tate, Jobe Alan H., Kallapur Suhas G.,and Chougnet Claire A., Effect of chorioamnionitis on regulatory T-cells in moderate/late preterm neonates. Hum. Immunol. 2015 January: 76(1): 65-73.Wing K., Larsson P., Sandstrom K., Lundin S.B., Suri-Payer E., et al. CD4+ CD25+ FOXP3+ regulatory T-cells from human thymus and cord blood suppress antigen-specific T-cell responses. Immunology. 2005; 115: 516-25.Mayer E., Bannert C., Gruber S., Klunker S., Spittler A., Akdis C.A., Szépfalusi Z., Eiwegger T. Cord blood derived CD4+ CD25high T-cells become functional regulatory T-cells upon antigen encounter. PLoS One. 2012; 7(1): e29355.Chang C.C., Satwani P., Oberfield N., Vlad G., Simpson L.L., et al. Increased induction of allogeneic-specific cord blood CD4+CD25+ regulatory T-(Treg) cells: a comparative study of naive and antigenic-specific cord blood Treg cells. Exp. Hematol. 2005; 33: 1508-20.Thornton C.A., Upham J.W., Wikstrom M.E., Holt B.J., White G.P., et al. Functional maturation of CD4+CD25+CTLA4+CD45RA+ T-regulatory cells in human neonatal T-cell responses to environmental antigens/allergens. J. Immunol. 2004; 173: 3084-92.Dirix V., Vermeulen F., Mascart F. Maturation of CD4+ regulatory T-lymphocytes and of cytokine secretions in infants born prematurely. J. Clin. Immunol. 2013; 33(6): 1126-33.Lin S.J., Lu C.H., Yan D.C., Lee P.T., Hsiao H.S., Kuo M.L. Expansion of regulatory T-cells from umbilical cord blood and adult peripheral blood CD4+CD25+ T-cells. Immunol. Res. 2014 Oct; 60(1): 105-11.Балашова Л.М., Быковская С.Н., Кузнецова Ю.Д., Коробова Л.С. Количественные и функциональные нарушения показателей клеточного иммунитета у взрослых, пожилых людей, соматически здоровых детей и больных ретинопатией недоношенных. Клиническая геронтология. 2012; 18(11-12): 76-7.Godfrey W.R., Spoden D.J., Ge Y.G., et al. Cord blood CD4+CD25+ derived T-regulatory cell lines express FoxP3 protein and manifest potent suppressor function. Blood. 2004; 105: 750-8.Mukhopadhyay D., Weaver L., Tobin R., Henderson S., Beeram M., Newell-Rogers M.K., Perger L.Intrauterine growth restriction and prematurity influence regulatory T-cell development in newborns. J. Pediatr. Surg. 2014 May; 49(5): 727-32.Misra R.S., Shah S., Fowell D.J., Wang H., Scheible K., Misra S.K., Huyck H., Wyman C.P., Ryan R.M., Reynolds A.M., Mariani T.J., Katzman P.J., Pryhuber G.S. Preterm cord blood CD4+ T-cells exhibit increased IL-6 production in chorioamnionitis and decreased CD4+ T-cells in bronchopulmonary dysplasia. Hum. Immunol. 2015 May; 76(5): 329-38.Bruder D., Westendorf A.M., Geffers R., Gruber A.D., Gereke M., Enelow R.I., Buer J. CD4 T-lymphocyte-mediated lung disease: steady state between pathological and tolerogenic immune reactions. Am. J. Respir. Crit. Care. Med. 2004; 170: 1145-52.Bokodi G., Treszl A., Kovács L., Tulassay T., Vásárhelyi B. Dysplasia: a review. Pediatr. Pulmonol. 2007 Oct; 42(10): 952-61.Hackam D.J., Afrazi A., Good M., Sodhi C.P. Innate Immune signaling in the Pathogenesis of necrotizing enterocolitis. Clin. Dev. Immunol. 2013; 2013: 475415.