REGULATORY T-CELLS IN CHILDREN WITH AUTOIMMUNE DISEASES
https://doi.org/10.15789/1563-0625-2014-4-353-360
Abstract
Children and teenagers aged 10-17 years old with juvenile arthritis (n=99), with reactive arthritis (n=21), with systemic sclerosis (n=16), with systemic lupus erythematosus (n=14) and conditionally healthy (n=32) are investigated. It’s revealed by the method of flow cytometry that quantity of regulatory T-cells (CD3+CD4+CD25+CD127low/neg) in children with juvenile arthritis, with reactive arthritis and with systemic
sclerosis was lower than in the control group. The amount of Treg in children with systemic lupus erythematosus was the same to the control level. The decrease of Treg number in most of investigated groups indicates that these cells are involved in the pathogenesis of an autoimmune diseases in children. It’s remaining unknown what’s the reason of normal Treg content in patients with systemic lupus erythematosus in contrast with other autoimmune diseases. There were positive correlation between the percentage of Treg and the amount of
damaged joints in children with reactive arthritis and negative correlation between the amount of Treg and SLEDAI in children with systemic lupus erythematosus. The significant correlations between the numbers of CD3+CD25+, CD3+CD4+CD25+ and Treg were revealed, so there isn’t any reasonability of estimation of CD3+ and CD4+cells which are expressed CD25 as separate parameters.
About the Author
I. A. Pashnina
Regional Children's Clinical Hospital №1, Yekaterinburg
Institute of Immunology and Physiology, Urals Branch of the Russian Academy of Science, Yekaterinburg
Russian Federation
Russian Federation
PhD, chef of Immunological laboratory of Immunological department, Regional Children's Clinical Hospital №1; research worker of Immunopathology laboratory, Institute of Immunology and Physiology, Urals Branch of the Russian Academy of Science
References
1. Козлов В.А., Борисов А.Г., Смирнова С.В., Савченко А.А. Практические аспекты диагностики и лечения иммунных нарушений: руководство для врачей. Новосибирск: Наука, 2009. 274 с. [Kozlov V.A., Borisov A.G., Smirnova S.V., Savchenko A.A. Prakticheskie aspekty diagnostiki i lecheniya immunnykh narusheniy: rukovodstvo dlya vrachey [Practical Aspects of Diagnostics and Treatment of Immune Malfunctions: Handbook for physician]. Novosibirsk: Science, 2009. 274 p.]
2. Криволапова И.М., Пашнина И.А., Скоробогатова О.В., Козлова Е.С. Спектр аутоантител у детей с ювенильным артритами и реактивным артритом // Вестник уральской медицинской академической науки. 2012. № 4 (41). С. 126-127. [Krivolapova I.M., Pashnina I.A., Skorobogatova O.V., Kozlova E.S. Spektr autoantitel u detey s yuvenil`nym artritami i reaktivnym artritom [Spectra of autoantibodies in children with juvenile arthritis and reactive arthritis]. Vestnik ural`skoy meditsinskoy akademicheskoy nauki = Bulletin of Ural Medical Academic Science, 2012, no. 4 (41), pp. 126-127.]
3. Пашнина И.А. Количество регуляторных Т-клеток у детей с ювенильными артритами // Российский иммунологический журнал. 2013. Т. 7 (16), № 2-3 (1). С. 74-76. [Pashnina I.A. Kolichestvo regulyatornykh T-kletok u detey s yuvenil`nymi artritami [The amount of regulatory T-cells in children with juvenile arthritis]. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2013, Vol. 7 (13), no. 2-3 (1), pp. 74-76.]
4. Пашнина И.А., Криволапова И.М., Козлова Е.С., Скоробогатова О.В., Тузанкина И.А., Черешнев В.А. Аутоантитела при ювенильных артритах у детей // Российский иммунологический журнал. 2013. Т.7 (16), № 4. С. 437-444. [Pashnina I.A., Krivolapova I.M., Kozlova E.S., Skorobogatova O.V., Tuzankina I.A., Chereshnev V.A. Autoantitela pri yuvenil`nykh artritakh u detey [Autoantibodies in children with juvenile arthritis ]. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2013, Vol. 7 (16), no. 4, pp. 437-444.]
5. Торгашина А.В., Быковская С.Ю., Соловьев С.К., Насонов Е.Л. Т регуляторные клетки при системной красной волчанке и ревматоидном артрите // Научно-практическая ревматология. 2009. № 3. С. 50-59. [Torgashina A.V., Bykovskaya S.Yu., Solov`ev S.K., Nasonov E.L. T regulyatornye kletki pri sistemnoy krasnoy volchanke i revmatoidnom artrite [T regulatory cells at rheumatoid arthritis and systemic lupus erythematosus]. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practiсе, 2009, no. 3, pp. 50-59.]
6. Хаитов Р.М., Пинегин Б.В., Ярилин А.А. Руководство по клинической иммунологии. Диагностика заболеваний иммунной системы: руководство для врачей. М.: ГЭОТАР-Медиа, 2009. 352 с. [Haitov R.M., Pinegin B.V., Yarilin A.A. Rukovodstvo po klinicheskoy immunologii. Diagnostika zabolevaniy immunnoy sistemy: rukovodstvo dlya vrachey [Handbook in Clinical Immunology: Diagnostics of Immune System Diseases: Handbook for physicians]. Moscow: GEOTAR-Media, 2009. 352 p.]
7. Alexander T., Sattler A., Templin L., Kohler S., Groß C., Meisel A., Sawitzki B., Burmester G.-R., Arnold R., Radbruch A., Thiel A., Hiepe F. FoxP3+ Helios+ regulatory T cells are expanded in active systemic lupus erythematosus. Ann. Rheum. Dis., 2013, Vol. 72, pp. 1549-1558. Alvarado-Sa´nchez B., Herna´ndez-Castro B., Portales-Pe´rez D., Baranda L., Layseca-Espinosa E., Abud-Mendoza C., Cubillas-Tejeda A.C., Gonza´lez-Amaro R. Regulatory T cells in patients with systemic lupus erythematosus. Journal of Autoimmunity, 2006, Vol. 27, pp. 110-118. Baecher-Allan, C., Brown J.A., Freeman G.J., Hafler D.A. CD4+CD25high regulatory cells in human peripheral blood. J. Immunol., 2001, Vol. 167, pp. 1245–1253.
8. Bennett C.L., Christie J., Ramsdell F., Brunkow M.E., Ferguson P.J., Whitesell L., Kelly T.E., Saulsbury F.T., Chance P.F., Ochs H.D. The immune dysregulation polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FoxP3. Nat. Genet., 2001, Vol. 27, no. 1, pp. 20-21.
9. Bonelli M., von Dalwigk K., Savitskaya A., Smolen J.S., Scheinecker C. FoxP3 expression in CD4+ T cells of patients with systemic lupus erythematosus: a comparative phenotypic analysis. Ann. Rheum. Dis., 2008, Vol. 67, pp. 664-671.
10. Cao D., Malmstrom V., Beacher-Allan C., Hafler D., Klareskog L., Trollmo C. Isolation and functional characterization of regulatory CD25brightCD4+T cells from the target organ of patients with rheumatoid arthritis. Eur. J. Immunol., 2003, Vol. 33, pp. 215-223.
11. Cao D., van Vollenhoven R., Klareskog L., Hafler D., Klareskog L., Trollmo C. CD25brightCD4+regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease. Arthritis. Res. Ther., 2004, Vol. 6, pp. 335-346.
12. Chunga I.Y., Dongb H.F., Zhangc X., Hassaneina N.M.A., Howarda O.M.Z., Oppenheima J.J., Chenb X. Effects of IL-7 and dexamethasone: Induction of CD25, the high affinity IL-2 receptor, on human CD4+ cells. Cellular Immunology, 2004, Vol. 232, Issues 1-2, pp. 57-63.
13. Coomes S.M., Pelly V.S., Wilson M.S. Plasticity within the ab+CD4+ T-cell lineage: when, how and what for? Open Biol., 2013, Vol. 3, pp. 120-157.
14. Ehrenstein M.R., Evans J.G., Singh A., Moore S., Warnes G., Isenberg D.A., Mauri C. Compromised function of regulatory t cells in rheumatoid arthritis and reversal by anti-TNF therapy. J. Exp. Med., 2004, Vol. 200, pp. 277-285.
15. Fazekas de StGroth B., Zhu E., Asad S., Lee L. Flow cytometric detection of human regulatory T cells. Regulatory T cells: Methods and protocols in Molecular Biology. Ed. Cassiotis G., Liston A. Springer Science+Business Media, 2011, Vol. 707, pp. 273-279.
16. Fenoglio D., Battaglia F., Parodi A., Stringara S., Negrini S., Panico N., Rizzi M., Kalli F., Conteducaa G., Ghio M., De Palmac R., Indiveri F., Filaci G. Alteration of Th17 and Treg cell subpopulations co-exist in patients affected with systemic sclerosis. Clinical Immunology, 2011, Vol. 139, pp. 249–257.
17. Han G.M., O’Neil-Andersen N.J., Zurier R.B., Lawrence D.A. CD4+CD25high T cell numbers are enriched in the peripheral blood of patients with rheumatoid arthritis. Cel. Immunol., 2008, Vol. 253, pp. 92-101.
18. Khattri R., Kasprowicz D., Cox T., Mortrud M., Appleby M.W., Brunkow M.E., Ziegler S.F., Ramsdell F. The amount of scurfin protein determines peripheral T-cell. Number and responsiveness. Journal of Immunology, 2001, Vol. 167, pp. 6312-6320.
19. Kleer I.M., Wedderburn L.R., Taams L.S., Patel A., Varsani H., Klein M., de Jager W., Pugayung G., Giannoni F., Rijkers G., Albani S., Kuis W., Prakken B. CD4+ CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J. Immunol., 2004, Vol. 172, pp. 6435-6443.
20. Lawson C.A., Brown A.K., Bejarano V.C., Douglas S.H., Burgoyne C.H., Greenstein A.S., Boylston A.W., Emery P., Ponchel1 F., Isaacset J.D. Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood. Rheumatology, 2006, Vol. 45, pp. 1210-1217.
21. Lee J.-H., Wang L.-C., Lin Y.-T., Yang Y.-H., Lin D.-T., Chiang B.-L. Inverse correlation between CD4+regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus. Immunology, 2006, Vol. 117, pp. 280-286.
22. Liu W., Putnam A.L., Xu-yu Z., Szot G.L., Lee M.R., Zhu S., Gottlieb P.A., Kapranov P., Gingeras T.R., Fazekas de St. Groth B., Clayberger C., Soper D.M., Ziegler S.F., Bluestone J.A. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ Treg cells. The Journal of Experimental Medicine, 2006, Vol. 203, no. 7, pp. 1701-1711.
23. Lyssuk E.Yu., Torgashina A.V., Soloviev S.K., Nassonov E.L., Bykovskaia S.N. Reduced Number and Function of CD4+CD25highFoxP3+ Regulatory T cells in patients with systemic lupus erythematosus. immunemediated diseases from theory to therapy. Ed. Shurin M.R., Smolkin Y.S. Springer Science+Business Media. Advanses in experimental medicine and biology, 2007, Vol. 601, pp. 113-119.
24. Miyara M., Amoura Z., Parizot C., Badoual C., Dorgham K., Trad S., Nochy D., Debre P., Piette J.C., Gorochov G. Global natural regulatory T cell depletion in active systemic lupus erythematosus. The Journal of Immunology, 2005, Vol. 175, pp. 8392-8400.
25. Morganа M.E., van Bilsen J.H., Bakker A.M., Heemskerk B., Schilham M.W., Hartgers F.C., Elferink B.G., van der Zanden L., de Vries R.R., Huizinga T.W., Ottenhoff T.H., Toes R.E. Expression of FoxP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans. Hum. Immunol., 2005, Vol. 66, pp. 3-20.
26. Mottonen M., Heikkinen J., Mustonen L., Isomäki P., Luukkainen R., Lassila O. CD4+CD25+ T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritis. Clin. Exp. Immunol., 2005, Vol. 140, pp. 360–367.
27. Nistala K., Moncrieffe H., Newton K.R., Varsani H., Hunter P., Wedderburn L.R. Interleukin-17–Producing T Cells Are Enriched in the Joints of Children With Arthritis, but Have a Reciprocal Relationship to Regulatory T Cell Numbers. Arthritis and Rheumatism, 2008, Vol. 58, pp. 875-887.
28. Radstake T.R.D.J., van Bon L., Broen J., Wenink M., Santegoets K., Deng Y., Hussaini A., Simms R., Cruikshank W.W., Lafyatis R. Increased frequency and compromised function of t regulatory cells in systemic sclerosis (SSc) is related to a diminished CD69 and TGFb expression. PLoS ONE, 2009, Vol. 4, Issue 6, p. 5981.
29. Sakaguchi S., Sakaguchi N., Asano M., Itoh M., Toda M. Immunologic tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol., 1995, Vol. 155, pp. 1151-1164.
30. Sakaguchi S., Takahashi T., Nishizuka Y. Study on cellular events in postthymectomy autoimmune oophoritis in mice. Requirement of Lyt-1 effector cells for oocytes damage after adoptive transfer. J. Exp. Med., 1982, Vol. 156, pp. 1565-1576.
31. Sfikakis P.P., Boletis J.N., Lionaki S., Vigklis V., Fragiadaki K.G., Iniotaki A., Moutsopoulos H.M. Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand. Arthritis and rheumatism, 2005, Vol. 52, no. 2, pp. 501-513.
32. Slobodin G., Ahmad M.S., Rosner I., Peri R., Rozenbaum M., Kessel A., Toubi E., Odeh M. Regulatory T cells (CD4+CD25brightFoxP3+) expansion in systemic sclerosis correlates with disease activity and severity. Cellular Immunology, 2010, Vol. 261, pp. 77-80.
33. Stelmaszczyk-Emmel A., Jackowska T., Rutkowska-Sak L., Marusak-Banacka M., Wasik M. Identification, frequency, activation and function of CD4+CD25highFoxP3+ regulatory T cells in children with juvenile idiopathic arthritis. Rheumatology, 2012, Vol. 32, pp. 1147-1154.
34. Sugihara S., Izumi Y., Yoshioka T., Yagi H., Tsujimura T., Tarutani O. Autoimmune thyroiditis induced in mice depleted of particular T-cell subset. Requirement of Lyt-1dull L3T4bright normal T cells for the induction of thyroiditis. J. Immunol., 1988, Vol. 141, pp. 105-113.
35. Valencia X., Yarboro C., Illei G., Lipsky P.E. Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J. Immunol., 2007, Vol. 178, pp. 2579-2588.
36. Van Amelsfort J.M., Jacobs K.M., Bijlsma J.W., Floris P.J., Lafeber G., Taams L.S. CD4+CD25+Regulatory T cells in rheumatoid arthritis. differences in the presence, phenotype and function between peripheral blood and synovial fluid. Arthritis & rheumatism, 2004, Vol. 50, no. 9, pp. 2775-2785.
37. Zhang Q., Cui F., Fang L., Hong J., Zheng B., Zhang J.Z. TNFα impairs differentiation and function of TGF-b-induced Treg cells in autoimmune diseases through Akt and Smad3 signaling pathway. Journal of Molecular Cell Biology, 2013, Vol. 5, pp. 85-98.
38. Ziegler S.F. FoxP3: Of Mice and Men. Annu. Rev. Immunol., 2006, Vol. 24, pp. 209-226.
Review
For citations:
Pashnina I.A. REGULATORY T-CELLS IN CHILDREN WITH AUTOIMMUNE DISEASES. Medical Immunology (Russia). 2014;16(4):353-360. (In Russ.) https://doi.org/10.15789/1563-0625-2014-4-353-360
Views:
1081
Email this article 