<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0873-2159</journal-id>
<journal-title><![CDATA[Revista Portuguesa de Pneumologia]]></journal-title>
<abbrev-journal-title><![CDATA[Rev Port Pneumol]]></abbrev-journal-title>
<issn>0873-2159</issn>
<publisher>
<publisher-name><![CDATA[Sociedade Portuguesa de Pneumologia]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0873-21592007000300005</article-id>
<title-group>
<article-title xml:lang="pt"><![CDATA[Células reguladoras]]></article-title>
<article-title xml:lang="en"><![CDATA[Regulatory cells]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Borrego]]></surname>
<given-names><![CDATA[Luís Miguel]]></given-names>
</name>
<xref ref-type="aff" rid="A01"/>
<xref ref-type="aff" rid="A02"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Rosa]]></surname>
<given-names><![CDATA[Sónia]]></given-names>
</name>
<xref ref-type="aff" rid="A01"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Algueró]]></surname>
<given-names><![CDATA[Cármen]]></given-names>
</name>
<xref ref-type="aff" rid="A02"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Trindade]]></surname>
<given-names><![CDATA[Hélder]]></given-names>
</name>
<xref ref-type="aff" rid="A02"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Pinto]]></surname>
<given-names><![CDATA[José Rosado]]></given-names>
</name>
<xref ref-type="aff" rid="A01"/>
<xref ref-type="aff" rid="A03"/>
</contrib>
</contrib-group>
<aff id="A03">
<institution><![CDATA[,Universidade Nova de Lisboa Faculdade de Ciências Médicas ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<aff id="A01">
<institution><![CDATA[,Hospital de Dona Estefânia Serviço de Imunoalergologia ]]></institution>
<addr-line><![CDATA[Lisboa ]]></addr-line>
</aff>
<aff id="A02">
<institution><![CDATA[,Universidade Nova de Lisboa Faculdade de Ciências Médicas Departamento de Imunologia]]></institution>
<addr-line><![CDATA[Lisboa ]]></addr-line>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>05</month>
<year>2007</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>05</month>
<year>2007</year>
</pub-date>
<volume>13</volume>
<numero>3</numero>
<fpage>365</fpage>
<lpage>376</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_arttext&amp;pid=S0873-21592007000300005&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_abstract&amp;pid=S0873-21592007000300005&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_pdf&amp;pid=S0873-21592007000300005&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="pt"><p><![CDATA[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.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[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.]]></p></abstract>
<kwd-group>
<kwd lng="pt"><![CDATA[Doenças alérgicas]]></kwd>
<kwd lng="pt"><![CDATA[células T reguladoras]]></kwd>
<kwd lng="pt"><![CDATA[tolerância periférica]]></kwd>
<kwd lng="en"><![CDATA[Allergic diseases]]></kwd>
<kwd lng="en"><![CDATA[peripheral tolerance]]></kwd>
<kwd lng="en"><![CDATA[regulatory T cells]]></kwd>
</kwd-group>
</article-meta>
</front><body><![CDATA[ <p><b>Células reguladoras</b></p>      <p><b>Regulatory cells</b></p>      <p>&nbsp;</p>      <p><b>Luís Miguel Borrego</b><sup><b><a href="#1">1</a><a name="top1"></a></b></sup></p>      <p><b>Sónia Rosa</b><sup><b><a href="#2">2</a><a name="top2"></a></b></sup></p>      <p><b>Cármen Algueró</b><sup><b><a href="#3">3</a><a name="top3"></a></b></sup></p>      <p><b>Hélder Trindade</b><sup><b><a href="#4">4</a><a name="top4"></a></b></sup></p>      <p><b>José Rosado Pinto</b><sup><b><a href="#5">5</a><a name="top5"></a></b></sup></p>      <p>&nbsp;</p>      <p align="center"><b>Resumo</b></p>      ]]></body>
<body><![CDATA[<p align="justify">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.</p>     <p align="justify"><b>Palavras-chave: </b>Doenças alérgicas, células T reguladoras,    tolerância periférica.</p>      <p>&nbsp;</p>      <p align="center"><b>Abstract</b></p>      <p align="justify">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.</p>     <p align="justify"><b>Key-words: </b>Allergic diseases, peripheral tolerance,    regulatory T cells.</p>      <p>&nbsp;</p>     <p>&nbsp;</p>      <p>Texto completo disponível apenas em PDF.</p>     <p>Full text only available in PDF format.</p>      ]]></body>
<body><![CDATA[<p>&nbsp;</p>     <p>&nbsp;</p>      <p align="center"><b>Bibliografia</b></p>      <!-- ref --><p>1. Baccheta R, Gregori S, Roncarolo MG. CD4+ regulatory T cells: Mechanisms of induction and effector function. Autoimmun Rev 2005; 4:491-6.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;[&#160;<a href="javascript:void(0);" onclick="javascript: window.open('/scielo.php?script=sci_nlinks&ref=000026&pid=S0873-2159200700030000500001&lng=','','width=640,height=500,resizable=yes,scrollbars=1,menubar=yes,');">Links</a>&#160;]<!-- end-ref --><p>2. Kay AB. Allergy and allergic diseases. N Engl J Med 2001;344:30-7.</p>      <p>3. El Biaze M, Boniface S, Koscher V, Mamessier E, Dupuy P, Milhe F <i>et al</i>. T cell activation, from atopy to asthma: more a paradox than a paradigm. Allergy 2003;58:844-53.</p>      <p>4. Mazzarella G, Bianco A, Catena E, De Palma R, Abbate GF. Th1/Th2 lymphocyte polarization in asthma. Allergy 2000;55(Suppl. 61):6-9.</p>      <p>5. Matricardi PM, Bouygue GR, Tripodi S. Inner-city asthma and the hygiene hypothesis. Ann Allergy Asthma Immunol 2002;89(6 Suppl 1):69-74.</p>      <p>6. Kalliomaki M, Isolauri E. Pandemic of atopic diseases – a lack of microbial exposure in early infancy? Curr Drug Targets Infect Disord 2002;2(3):193-9.</p>      <p>7. Matricardi PM. The role of early infections, hygiene and intestinal microflora. Pediatr Pulmonol Suppl 2004;26:211-2.</p>      ]]></body>
<body><![CDATA[<p>8. Akbari O, Stock P, DeKruyff RH, Umetsu D. Role of regulatory T cells in allergy and asthma. Curr Opin Immunol 2003; 15:627-33.</p>      <p>9. Maggi E, Cosmi L, Liotta F, Romagnani P, Romagnani S, Annunziato F. Thymic regulatory T cell. Autoimmun Rev 2005; 4:579-86.</p>      <p>10. Hauben E, Roncarolo MG. Human CD4+ regulatory T cells and activation-induced tolerance. Microbes Infect 2005; 7:1023-32.</p>      <p>11. Baecher-Allan C, Hafler DA. Suppressor T Cells in Human Diseases. J Exp Med 2004;200(3):273-276.</p>      <p>12. Danke NA, Koelle DM, Yee C, Beheray S, Kwok WW. Autoreactive T cells in healthy individuals. J Immunol 2004;172:5967-72.</p>      <p>13. Chen Y, Kuchroo VK, Inobe J, Hafler DA, Weiner HL. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 1994;265(5176):1237-40.</p>      <p>14. Lan RY, Ansari AA, Lian ZX, Gershwin ME. Regulatory T cells: Development, function and role in autoimmunity. Autoimmun Rev 2005,4:351-63.</p>      <p>15. Groux H, O’Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, Roncarolo MG. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997;389(6652):737-42.</p>      <p>16. Steinbrink K, Graulich E, Kubsch S, Knop J, Enk AH. CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood 2002;99(7):2468-76.</p>      <p>17. Akbari <i>et al</i>. Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Med 2002; 8:1024-32.</p>      ]]></body>
<body><![CDATA[<p>18. Stock P, Akbari O, Berry G, Freeman GJ, Dekruyff RH, Umetsu DT. Induction of T helper type 1-like regulatory cells that express Foxp3 and protect against airway hiperreactivity. Nat Immunol 2004; 5:149-56.</p>      <p>19. Itoh M, Takahashi T, Sakaguchi N, Kuniyasu Y, Shimizu J, Otsuka F <i>et al</i>. 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 1999;162:5317-26.</p>      <p>20. Akbari O, Stock P, Meyer E, Kronenberg M, Sidobre S, Nakayama T, Taniguchi M, Grusby MJ, DeKruyff RH, Umetsu DT. Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Nat Med 2003;9(5):582-8. Epub 2003 Mar 31.</p>      <p>21. Kuniyasu Y, Takahashi T, Itoh M, Shimizu J, Toda G, Sakaguchi S. Naturally anergic and suppressive CD25+CD4+ T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulation. Int Immunol 2000;12:1145-55.</p>      <p>22. Suri-Payer E, Amar AZ, Thornton AM, Shevach EM. 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 1998;160:1212-1218. 992</p>      <p>23. Misra N, Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Kaveri SV. Cuttingedge: human CD4+CD25+ T cells restrain the maturation and antigenpresenting function of dendritic cells. J Immunol 2004;172:4676-80.</p>      <p>24. Grossman WJ, Verbsky JW, Barchet W, Colonna M, Atkinson JP, Ley TJ. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 2004;21:589-601.</p>      <p>25. Thornton AM, Shevach EM. Suppressor effector function of CD25+CD4+ immunoregulatory T cells is antigen nonspecific. J Immunol 2000;164:183-90.</p>      <p>26. Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F. An essential role for interleukin 10 in the function oh regulatory T cells that inhibit intestinal inflammation. J Exp Med 1999;190: 995-1004.</p>      <p>27. Powrie F, Carlino J, Leach MW, Mauze S, Coffman RL. 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 1996;183:2669-74.</p>      ]]></body>
<body><![CDATA[<p>28. de la Rosa M, Rutz S, Dorninger H, Scheffold A. Interleukin-2 is essential for CD4+CD25+ regulatory T cell function. Eur J Immunol 2004;34:2480-88.</p>      <p>29. Zheng SG, Wang JH, Gray JD, Soucier H, Horwitz DA. 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 2004;172:5213-21.</p>      <p>30. Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S. Stimulation oh CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 2002;3:135-42.</p>      <p>31. McHugh RS, Whitters MJ, Piccirillo CA, Young DA, Shevach EM, CollinsM <i>et al</i>. CD25+CD4+ immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoidinduced TNF receptor. Immunity 2002;16:311-23.</p>      <p>32. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD25+CD4+ regulatory T cells. Nat Immunol 2003;4: 330-6.</p>      <p>33. Khattri R, Cox T, Yasayko S-A, Ramsdell F. An essential role for Scurfin in CD25+CD4+ T regulatory T cells. Nat Immunol 2003;4:337-42.</p>      <p>34. Morgan ME, van Bilsen JH, Bakker AM, Heemskerk B, Schilham MW, Hartgers FC <i>et al</i>. Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans. Hum Immunol 2005;66:13-20.</p>      <p>35. Fu S, Zhang N, Yopp AC, Chen D, Mão M, Chen D <i>et al</i>. TGF-â induces Foxp3+ T regulatory cells from CD4+CD25) precursors. Am J Transplant 2004;4:1614-27.</p>      <p>36. Zheng Y, Manzotti CN, Liu M, BurkeF, Mead KI, Sansom DM. CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells. J Immunol 2004;172:2778-84.</p>      <p>37. Liang S, Alard P, Zhao Y, Parnell S, Clark SL, Kosiewicz MM. Conversion oh CD4+CD25) cells into CD4+CD25+regulatory T cells <i>in vivo </i>requires B7 costimulation, but not the thymus. J Exp Med 2005;201:127-37.</p>      ]]></body>
<body><![CDATA[<p>38. Tang Q, Boden EK, Henriksen KJ, Bour-Jordan H, Bi M, Bluestone JA. Distinct roles of CTLA-4 and TGF-â in CD4+CD25+ regulatory T cell function. Eur J Immunol 2004;34:2996-3005.</p>      <p>39. Paust S, Lu L, McCarty N, Cantor H. Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc Natl Acad Sci USA 2004;101:10398-403.</p>      <p>40. Zheng G, Wang B, Chen A. The 4-1BB costimulation augments the proliferation of CD4+CD25+ regulatory T cells. J Immunol 2004;173:2428-34.</p>      <p>41. Bruder D, Probst-Kepper M, Westendorf AM, Geffers R, Beissert S, Loser K <i>et al</i>. Neuropilin-1: a surface marker of regulatory T cells. Eur J Immunol 2004;34:623-30.</p>      <p>42. Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G <i>et al</i>. Role oh LAG-3 in regulatory T cells. Immunity 2004;21:503-13.</p>      <p>43. Bopp T, Palmetshofer A, Serfling E, Heib V, Schmitt S, Richter C <i>et al</i>. NFATc2 and NFATc3 transcription factors play a crucial role in suppression of CD4+ T lymphocytes by CD4+CD25+ regulatory T cells. J Exp Med 2005;201:181-7.</p>      <p>44. Gambineri E, Torgerson T, Ochs H. 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 2003; 15:430-5.</p>      <p>45. Hansen G, McIntire JJ, Yeung VP, Berry G, Thorbecke GJ, Chen L, DeKruyff RH, Umetsu DT. CD4(+) T helper cells engineered to produce latent TGF-beta1 reverse allergen-induced airway hyperrreactivity and inflammation. J Clin Invest 2000; 105:61-70.</p>      <p>&nbsp;</p>      <p><sup><a href="#top1">1</a><a name="1"></a></sup> Assistente Hospitalar de Imunoalergologia.    Serviço de Imunoalergologia do Hospital de Dona Estefânia. Assistente Convidado    do Departamento de Imunologia da Faculdade de Ciências Médicas de Lisboa.</p>      ]]></body>
<body><![CDATA[<p><sup><a href="#top2">2</a><a name="2"></a></sup> Interna do Internato Complementar    de Imunoalergologia. Serviço de Imunoalergologia do Hospital de Dona Estefânia.</p>      <p><sup><a href="#top3">3</a><a name="3"></a></sup> Assistente Convidada do Departamento    de Imunologia da Faculdade de Ciências Médicas de Lisboa.</p>      <p><sup><a href="#top4">4</a><a name="4"></a></sup> Professor Associado Convidado    com Agregação do Departamento de Imunologia da Faculdade de Ciências Médicas    de Lisboa.</p>      <p><sup><a href="#top5">5</a><a name="5"></a></sup> Responsável pelo Serviço de    Imunoalergologia do Hospital de Dona Estefânia. Professor Auxiliar convidado    da Faculdade de Ciências Médicas de Lisboa.</p>      <p>&nbsp;</p>      <p>Serviço de Imunoalergologia – Hospital de Dona Estefânia:</p>      <p>Rua Jacinta Marto – 169-045 Lisboa – E-mail: <a href="mailto:hde.imunoalergo@mail.telepac.pt">hde.imunoalergo@mail.telepac.pt</a>    – Tel: +351213126600 / Fax: +351213126654</p>      <p>Faculdade de Ciências Médicas - Universidade Nova de Lisboa:</p>      <p>Departamento de Imunologia, Campo dos Mártires da Pátria, n.º 130 1169-056 Lisboa <b>– </b>Tel: 351-218803045/ 218853000 / Fax: 218853480</p>      <p>&nbsp;</p>      ]]></body>
<body><![CDATA[<p>Recebido para publicação/received for publication : 06.11.23</p>     <p>Aceite para publicação/accepted for publication : 07.02.20</p>       ]]></body><back>
<ref-list>
<ref id="B1">
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Baccheta]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Gregori]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Roncarolo]]></surname>
<given-names><![CDATA[MG.]]></given-names>
</name>
</person-group>
<article-title xml:lang="en"><![CDATA[CD4+ regulatory T cells: Mechanisms of induction and effector function.]]></article-title>
<source><![CDATA[Autoimmun Rev]]></source>
<year>2005</year>
<volume>4</volume>
<page-range>491-6</page-range></nlm-citation>
</ref>
</ref-list>
</back>
</article>
