Article information
Resumo
O papel das células T reguladoras na indução e manutenção da tolerância periférica tem recebido uma atenção crescente nos últimos anos. Foram descritos vários subgrupos de células T reguladoras, com base em marcadores de superfície e na produção de citocinas, não havendo no entanto marcadores específicos para nenhum destes subgrupos, pelo que a sua classificação se baseia no seu mecanismo de supressão.
Desconhece-se qual dos subgrupos de células T reguladoras terá papel preponderante na prevenção e controlo das doenças alérgicas, sendo no entanto consensual a sua importância para a homeostasia.
Palavras-chave:
Doenças alérgicas
células T reguladoras
tolerância periférica
Abstract
The role of regulatory T cells in the induction and maintenance of peripheral tolerance has received growing attention during the last years. Several subsets of regulatory T cells were described based on their surface markers and citokine production, but nevertheless, there are no specific markers for any subsets and their classification relies on their suppression mechanism.
It is unknown which of the subgroups of regulatory T cells is more important in the prevention and control of allergic diseases, being commonly accepted its importance in homeostasis.
Key-words:
Allergic diseases
peripheral tolerance
regulatory T cells
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Bibliografia
[1.]
R. Baccheta, S. Gregori, M.G. Roncarolo.
CD4+ regulatory T cells: Mechanisms of induction and effector function.
Autoimmun Rev, 4 (2005), pp. 491-496
[2.]
A.B. Kay.
Allergy allergic diseases.
N Engl J Med, 344 (2001), pp. 30-37
[3.]
M. El Biaze, S. Boniface, V. Koscher, E. Mamessier, P. Dupuy, F. Milhe, et al.
T cell activation, from atopy to asthma: more a paradox than a paradigm.
Allergy, 58 (2003), pp. 844-853
[4.]
G. Mazzarella, A. Bianco, E. Catena, R. De Palma, G.F. Abbate.
Th1/Th2 lymphocyte polarization in asthma.
Allergy, 55 (2000), pp. 6-9
[5.]
P.M. Matricardi, G.R. Bouygue, S. Tripodi.
Inner-city asthma and the hygiene hypothesis.
Ann Allergy Asthma Immunol, 89 (2002), pp. 69-74
[6.]
M. Kalliomaki, E. Isolauri.
Pandemic of atopic diseases – a lack of microbial exposure in early infancy?.
Curr Drug Targets Infect Disord, 2 (2002), pp. 193-199
[7.]
P.M. Matricardi.
The role of early infections, hygiene and intestinal microflora.
Pediatr Pulmonol Suppl, 26 (2004), pp. 211-212
[8.]
O. Akbari, P. Stock, R.H. DeKruyff, D. Umetsu.
Role of regulatory T cells in allergy and asthma.
Curr Opin Immunol, 15 (2003), pp. 627-633
[9.]
E. Maggi, L. Cosmi, F. Liotta, P. Romagnani, S. Romagnani, F. Annunziato.
Thymic regulatory T cell.
Autoimmun Rev, 4 (2005), pp. 579-586
[10.]
E. Hauben, M.G. Roncarolo.
Human CD4+ regulatory T cells and activation-induced tolerance.
Microbes Infect, 7 (2005), pp. 1023-1032
[11.]
C. Baecher-Allan, D.A. Hafler, T. Suppressor.
Cells in Human Diseases.
J Exp Med, 200 (2004), pp. 273-276
[12.]
N.A. Danke, D.M. Koelle, C. Yee, S. Beheray, W.W. Kwok, T. Autoreactive.
cells in healthy individuals.
J Immunol, 172 (2004), pp. 5967-5972
[13.]
Y. Chen, V.K. Kuchroo, J. Inobe, D.A. Hafler, H.L. Weiner, T. Regulatory.
cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis.
Science, 265 (1994), pp. 1237-1240
[14.]
R.Y. Lan, A.A. Ansari, Z.X. Lian, M.E. Gershwin, Regulatory T.
cells: Development, function and role in autoimmunity.
Autoimmun Rev, 4 (2005), pp. 351-363
[15.]
H. Groux, A. O’Garra, M. Bigler, M. Rouleau, S. Antonenko, J.E. de Vries, M.G. Roncarolo.
A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis.
Nature, 389 (1997), pp. 737-742
[16.]
K. Steinbrink, E. Graulich, S. Kubsch, J. Knop, A.H. Enk.
CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity.
Blood, 99 (2002), pp. 2468-2476
[17.]
Akbari, et al.
Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity.
Nat Med, 8 (2002), pp. 1024-1032
[18.]
P. Stock, O. Akbari, G. Berry, G.J. Freeman, R.H. Dekruyff, D.T. Umetsu.
Induction of T helper type 1-like regulatory cells that express Foxp3 and protect against airway hiperreactivity.
Nat Immunol, 5 (2004), pp. 149-156
[19.]
M. Itoh, T. Takahashi, N. Sakaguchi, Y. Kuniyasu, J. Shimizu, F. Otsuka, et al.
Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance.
J Immunol, 162 (1999), pp. 5317-5326
[20.]
O. Akbari, P. Stock, E. Meyer, M. Kronenberg, S. Sidobre, T. Nakayama, M. Taniguchi, M.J. Grusby, R.H. DeKruyff, D.T. Umetsu.
Essential role of NKT cells producing IL- 4 and IL-13 in the development of allergen-induced airway hyperreactivity.
Nat Med, 9 (2003), pp. 582-588
[21.]
Y. Kuniyasu, T. Takahashi, M. Itoh, J. Shimizu, G. Toda, S. Sakaguchi.
Naturally anergic and suppressive CD25+CD4+ T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulation.
Int Immunol, 12 (2000), pp. 1145-1155
[22.]
E. Suri-Payer, A.Z. Amar, A.M. Thornton, E.M. Shevach.
CD4+CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells.
J Immunol, 160 (1998), pp. 1212-1218
[23.]
N. Misra, J. Bayry, S. Lacroix-Desmazes, M.D. Kazatchkine, S.V. Kaveri.
Cuttingedge: human CD4+CD25+ T cells restrain the maturation and antigenpresenting function of dendritic cells.
J Immunol, 172 (2004), pp. 4676-4680
[24.]
W.J. Grossman, J.W. Verbsky, W. Barchet, M. Colonna, J.P. Atkinson, T.J. Ley, T. Human.
regulatory cells can use the perforin pathway to cause autologous target cell death.
Immunity, 21 (2004), pp. 589-601
[25.]
A.M. Thornton, E.M. Shevach.
Suppressor effector function of CD25+CD4+ immunoregulatory T cells is antigen nonspecific.
J Immunol, 164 (2000), pp. 183-190
[26.]
C. Asseman, S. Mauze, M.W. Leach, R.L. Coffman, F. Powrie.
An essential role for interleukin 10 in the function oh regulatory T cells that inhibit intestinal inflammation.
J Exp Med, 190 (1999), pp. 995-1004
[27.]
F. Powrie, J. Carlino, M.W. Leach, S. Mauze, R.L. Coffman.
A critical role for transforming growth factor b but not interleukin 4 in the suppression of T helper type 1 mediated colitis by CD45RBlow CD4+ T cells.
J Exp Med, 183 (1996), pp. 2669-2674
[28.]
M. de la Rosa, S. Rutz, H. Dorninger, A. Scheffold.
Interleukin-2 is essential for CD4+CD25+ regulatory T cell function.
Eur J Immunol, 34 (2004), pp. 2480-2488
[29.]
S.G. Zheng, J.H. Wang, J.D. Gray, H. Soucier, D.A. Horwitz.
Natural and induced CD4+CD25+ cells educate CD4+CD25) cells to develop suppressive activity: the role of IL-2 TGF-b, and IL-10.
J Immunol, 172 (2004), pp. 5213-5221
[30.]
J. Shimizu, S. Yamazaki, T. Takahashi, Y. Ishida, S. Sakaguchi.
Stimulation oh CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance.
Nat Immunol, 3 (2002), pp. 135-142
[31.]
R.S. McHugh, M.J. Whitters, C.A. Piccirillo, D.A. Young, E.M. Shevach, M. Collins, et al.
CD25+CD4+ immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoidinduced TNF receptor.
Immunity, 16 (2002), pp. 311-323
[32.]
J.D. Fontenot, M.A. Gavin, A.Y. Rudensky.
Foxp3 programs the development and function of CD25+CD4+ regulatory T cells.
Nat Immunol, 4 (2003), pp. 330-336
[33.]
R. Khattri, T. Cox, S.-A. Yasayko, F. Ramsdell.
An essential role for Scurfin in CD25+CD4+ T regulatory T cells.
Nat Immunol, 4 (2003), pp. 337-342
[34.]
M.E. Morgan, J.H. van Bilsen, A.M. Bakker, B. Heemskerk, M.W. Schilham, F.C. Hartgers, et al.
Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans.
Hum Immunol, 66 (2005), pp. 13-20
[35.]
S. Fu, N. Zhang, A.C. Yopp, D. Chen, M. Mão, D. Chen, et al.
TGF-β induces Foxp3+ T regulatory cells from CD4+CD25) precursors.
Am J Transplant, 4 (2004), pp. 1614-1627
[36.]
Y. Zheng, C.N. Manzotti, M. Liu, BurkeF, K.I. Mead, D.M. Sansom.
CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells.
J Immunol, 172 (2004), pp. 2778-2784
[37.]
S. Liang, P. Alard, Y. Zhao, S. Parnell, S.L. Clark, M.M. Kosiewicz.
Conversion oh CD4+CD25) cells into CD4+CD25+ regulatory T cells in vivo requires B7 costimulation, but not the thymus.
J Exp Med, 201 (2005), pp. 127-137
[38.]
Q. Tang, E.K. Boden, K.J. Henriksen, H. Bour-Jordan, M. Bi, J.A. Bluestone.
Distinct roles of CTLA-4 and TGF-β in CD4+CD25+ regulatory T cell function.
Eur J Immunol, 34 (2004), pp. 2996-3005
[39.]
S. Paust, L. Lu, N. McCarty, H. Cantor.
Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease.
Proc Natl Acad Sci USA, 101 (2004), pp. 10398-10403
[40.]
G. Zheng, B. Wang, A. Chen.
The 4-1BB costimulation augments the proliferation of CD4+CD25+ regulatory T cells.
J Immunol, 173 (2004), pp. 2428-2434
[41.]
D. Bruder, M. Probst-Kepper, A.M. Westendorf, R. Geffers, S. Beissert, K. Loser, et al.
Neuropilin-1: a surface marker of regulatory T cells.
Eur J Immunol, 34 (2004), pp. 623-630
[42.]
C.T. Huang, C.J. Workman, D. Flies, X. Pan, A.L. Marson, G. Zhou, et al.
Role oh LAG-3 in regulatory T cells.
Immunity, 21 (2004), pp. 503-513
[43.]
T. Bopp, A. Palmetshofer, E. Serfling, V. Heib, S. Schmitt, C. Richter, et al.
NFATc2 and NFATc3 transcription factors play a crucial role in suppression of CD4+ T lymphocytes by CD4+CD25+ regulatory T cells.
J Exp Med, 201 (2005), pp. 181-187
[44.]
E. Gambineri, T. Torgerson, H. Ochs.
Immune dysregulation . polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of Foxp3, a critical regulator of T cell homeostasis.
Curr Opin Rheumatol, 15 (2003), pp. 430-435
[45.]
G. Hansen, J.J. McIntire, V.P. Yeung, G. Berry, G.J. Thorbecke, L. Chen, R.H. DeKruyff, D.T. Umetsu.
CD4(+) T helper cells engineered to produce latent TGF-beta1 reverse allergen-induced airway hyperrreactivity and inflammation.
J Clin Invest, 105 (2000), pp. 61-70
[46.]
J.W. Oh, C.M. Seroogy, E.H. Meyer, O. Akbari, G. Berry, C.G. Fathman, R.H. DeKruyff, D.T. Umetsu.
CD4 T- helper cells engineered to produce IL-10 prevent allergeninduced airway hyperrreactivity and inflammation.
J Allergy Clin Immunol, 110 (2002), pp. 460-468
[47.]
D.T. Umetsu, O. Akbari, R.H. Dekruyff.
Regulatory T cells control the development of allergic diseases and asthma.
J Allergy Clin Immunol, 112 (2003), pp. 480-487
[48.]
X. Zhang, L. Izikson, L. Liu, H.L. Weiner.
Activation of CD25+CD4+ regulatory T cells by oral antigen administration.
J Immunol, 147 (2001), pp. 4245-4253
[49.]
M.R. Karlsson, J. Rugtveit, P. Brandtzaeg.
Allergen-responsive CD4+CD25+ regulatory T cells in children who have outgrown cow's milk allergy.
J Exp Med, 199 (2004), pp. 1679-1688
[50.]
L.S. Ou, E. Goleva, C. Hall, D.Y. Leung.
T regulatory cells in atopic dermatitis and subversion of their activity by superantigens.
J Allergy Clin Immunol, 113 (2004), pp. 756-763
[51.]
E.M. Ling, T. Smith, X.D. Nguyen, C. Pridgeon, M. Dallman, J. Arbery, et al.
Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease.
Lancent, 363 (2004), pp. 608-615
[52.]
H. Grindebacke, K. Wing, A.C. Andersson, E. Suri-Payer, S. Rak, A. Rudin.
Defective suppression of Th2 cytokines by CD4+CD25+ regulatory T cells in birch allergics during birch pollen season.
Clin Exp Allergy, 34 (2004), pp. 1364-1372
[53.]
A. Doganci, et al.
The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo.
J Clin Invest, 115 (2005), pp. 313-325
[54.]
A. Suto, H. Nakajima, S.I. Kagami, K. Suzuki, Y. Saito, I. Iwamoto.
Role of CD4+CD25+ regulatory T cells in T helper 2 cell-mediated allergic inflammation in the airways.
Am J Respir Crit Care Med, 164 (2001), pp. 680-687
[55.]
Z. Jaffar, T. Sivakuru, K. Roberts.
CD4+CD25+ T cells regulate airway eosinophilic inflammation by modulating the Th2 cell phenotype.
J Immunol, 172 (2004), pp. 3842-3849
[56.]
P. Stock, O. Akbari, G. Berry, G.J. Freeman, R.H. Dekruyff, D.T. Umetsu.
Induction of T helper type 1-like regulatory cells that express Foxp3 and protect against airway hyperreactivity.
Nat Immunol, 5 (2004), pp. 1149-1156
[57.]
H.Z. Shi, S. Li, Z.F. Xie, X.J. Qin, X. Qin, X.N. Zhong.
Regulatory CD4+CD25+ T lymphocytes in peripheral blood from patients with atopic asthma.
Clin Immunol, 113 (2004), pp. 172-178
[58.]
Unni Haddeland, et al.
Putative regulatory T cells are impaired in cord blood from neonates with hereditary allergy risk.
Pediatr Allergy Immunol, 16 (2005), pp. 104-112
[59.]
P.J. Barnes.
Molecular mechanisms of glucocorticoid action in asthma.
J Allergy Clin Immunol, 97 (1996), pp. 159-168
[60.]
R. Djukanovic, J.W. Wilson, K.M. Britten, S.J. Wilson, A.F. Walls, W.R. Roche, et al.
Effect of an inhaled glucocorticoid of airway inflammation and symptoms in asthma.
Am Rev Respir Dis, 145 (1992), pp. 669-674
[61.]
R.J. Meijer, H.A. Kerstjens, L.R. Arends, H.F. Kauffman, G.H. Koeter, D.S. Postma.
Effects of inhaled fluticasone and oral prednisolone on clinical and inflammatory parameters in patients with asthma.
Thorax, 54 (1999), pp. 894-899
[62.]
X. Chen, T. Murakami, J.J. Oppenheim, O.M.Z. Howard.
Differential response of murine CD4+CD25+ and CD4+CD25) T cells to dexamethasone-induced cell death.
Eur J Immunol, 34 (2004), pp. 859-869
[63.]
X.D. Nguyen, D.S. Robinson.
Fluticasone propionate increases CD4+CD25+ T regulatory cell suppression of allergenstimulated CD4+CD25) T cells by na IL-10 dependent mechanism.
J Allergy Clin Immunol, 114 (2004), pp. 296-301
[64.]
C. Karagiannidis, M. Akdis, P. Holopainen, N.J. Woolley, G. Hense, B. Rückert, et al.
Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma.
J Allergy Clin Immunol, 114 (2004), pp. 1425-1433
[65.]
S.J. Till, S.R. Durham.
Immunological responses to allergen immunotherapy.
Clin Allergy Immunol, 18 (2004), pp. 85-104
[66.]
S.J. Till, J.N. Francis, K. Nouri-Aria, S.R. Durham.
Mechanisms of immunotherapy.
J Allergy Clin Immunol, 113 (2004), pp. 1025-1034
[67.]
C.A. Akdis, K. Blaser, M. Akdis.
Genes oh tolerance.
Allergy, 59 (2004), pp. 897-913
[68.]
V.A. Varney, M. Gaga, A.J. Frew, V.R. Aber, A.B. Kay, S.R. Durham.
Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs.
BMJ, 302 (1991), pp. 265-299
[69.]
J. Bousquet, P. Calvayrac, B. Guerin, A. Hejjaoui, H. Dhivert, B. Hewitt, et al.
Immunotherapy with a standardized Dermatophagoides pteronyssinus extract I. In vivo and in vitro parameters after a short course of treatment.
J Allergy Clin Immunol, 76 (1985), pp. 734-744
[70.]
V.A. Varney, J. Edwards, K. Tabbah, H. Brewster, G. Mavroleon, A.J. Frew.
Clinical efficacy of specific immunotherapy to cat dander: a double-blind placebo-controlled trial.
Clin Exp Allergy, 13 (1960), pp. 27-33
[72.]
C. Möller, S. Dreborg, H.A. Ferdousi, et al.
Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study).
J Allergy and Clin Immunol, 109 (2002), pp. 251-256
[73.]
A. Des Roches, L. Paradis, J.L. Menardo, et al.
Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitization in children.
J Allergy Clin Immunol, 99 (1997), pp. 450-453
[74.]
M. Jutel, M. Akdis, F. Budak, et al.
IL-10 and TGF-β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy.
European Journal of Immunology, 33 (2003), pp. 1205-1214
[75.]
O. Akbari, et al.
Essential role of NKT cells producing IL-4 and IL-13 in the development of airway allergeninduced airway hyperrreactivity.
Nat Med, 9 (2003), pp. 582-588
[76.]
O. Akbari, R.H. DeKruyff, D.T. Umetsu.
Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to the antigen.
Nat Immunol, 2 (2001), pp. 725-731
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