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        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">A coordena&#231;&#227;o das caracter&#237;sticas humorais e celulares da resposta al&#233;rgica&#44; sabe-se hoje&#44; est&#225; dependente da regula&#231;&#227;o por linf&#243;citos T&#46; As vacinas de alerg&#233;nios s&#227;o uma terap&#234;utica que consegue modular a resposta das c&#233;lulas T&#44; e cujos mecanismos imunol&#243;gicos permanecem incompletamente esclarecidos&#46;</p><p id="sp0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Objectivo&#58;</span> Avaliar o efeito da imunoterapia&#44; ap&#243;s um ano de tratamento&#44; na express&#227;o de citocinas de perfil T1 e T2 em linf&#243;citos de sangue perif&#233;rico de doentes at&#243;picos&#46;</p><p id="sp0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Material e m&#233;todos&#58;</span> Estudaram-se dez doentes at&#243;picos sensibilizados a aeroalerg&#233;nios comuns a fazerem vacinas de alerg&#233;nios num per&#237;odo m&#233;dio de um ano&#46; Dentre estes&#44; seis foram estudados antes e ap&#243;s a vacina&#46; Como controlo estudou-se um grupo at&#243;pico sem imunoterapia constitu&#237;do por 14 doentes tamb&#233;m sensibilizados a aeroalerg&#233;nios comuns e um grupo de indiv&#237;duos n&#227;o at&#243;picos&#44; saud&#225;veis&#44; constitu&#237;do por 7 elementos&#46; A activa&#231;&#227;o dos linf&#243;citos T fez-se com PMA&#44; ionomicina e brefeldina e estudaram-se as citocinas intracitoplasm&#225;ticas IFN-&#947;&#44; IL-4&#44; IL-5 e IL-10 por citometria de fluxo&#46; Procedeu-se a an&#225;lise estat&#237;stica por testes n&#227;o param&#233;tricos &#40;Teste de Mann-Whitney U e Wilcoxon&#41;&#44; considerando-se significativo p<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Resultados&#58;</span> A express&#227;o de IL-4 e IL-5 nas c&#233;lulas T&#44; caracteristicamente aumentada nos doentes at&#243;picos&#44; respectivamente 13&#44;8 &#40;3&#44;1-31&#44;8&#41; e 6&#44;7&#37; &#40;1&#44;0-20&#44;4&#41;&#44; &#233; significativamente mais baixa no grupo que realizou a imunoterapia &#91;5&#44;4 &#40;2&#44;9-15&#44;6&#41; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007 e 2&#44;1&#37; &#40;0&#44;6-4&#44;8&#41; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;035&#93; n&#227;o diferindo do grupo controlo n&#227;o at&#243;pico &#91;5&#44;1 &#40;4&#44;1-6&#44;9&#41; e 1&#44;0 &#40;0&#44;4-2&#44;1&#41;&#93;&#46; Os n&#237;veis de IFN-&#947; n&#227;o variaram significativamente entre os tr&#234;s grupos estudados&#44; mas a raz&#227;o IFN-&#947;&#47; &#47;IL-4 nos linf&#243;citos T CD4 aumentou significativamente nos doentes submetidos a imunoterapia&#46; Por outro lado&#44; houve um aumento da express&#227;o de IL-10 nas c&#233;lulas T circulantes do grupo sob imunoterapia&#44; comparativamente a controlos n&#227;o at&#243;picos &#91;1&#44;9 &#40;1&#44;0-4&#44;9&#41; <span class="elsevierStyleItalic">versus</span> 1&#44;4&#37; &#40;0&#44;9-1&#44;4&#41; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#93;&#44; sendo mais evidente nos linf&#243;citos T CD8&#46; A IL-10 correlacionou-se de forma significativa com todas as citocinas de perfil T2 &#40;IL-4 e IL-5&#41; e com o fen&#243;tipo Tc2&#46;</p><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Conclus&#227;o&#58;</span> Ap&#243;s um ano de imunoterapia&#44; a resposta das c&#233;lulas T do sangue perif&#233;rico a uma estimula&#231;&#227;o policlonal evidenciou uma diminui&#231;&#227;o da express&#227;o das citocinas &#40;IL-4 e IL-5&#41;&#44; caracteristicamente aumentadas na doen&#231;a al&#233;rgica&#46; O aumento da IL-10&#44; que tamb&#233;m verific&#225;mos&#44; sugere a exist&#234;ncia de uma popula&#231;&#227;o reguladora de perfil T2&#44; sendo mais evidente nos linf&#243;citos T CD8&#46;</p><p id="sp0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Rev Port Pneumol 2006&#59; XII &#40;2&#41;&#58; 107-130</span></p></span>"
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        "resumen" => "<span id="as0010" class="elsevierStyleSection elsevierViewall"><p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">Allergen-specific immunotherapy has been used for successful treatment of atopic diseases&#46; They may act by modifying the patterns of cytokines produced by T cells&#46; However&#44; the precise mechanism by which it accomplishes these effects is still incompletely understood&#46;</p><p id="sp0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Objective&#58;</span> To evaluate the effect of one year immunotherapy on cytokines profiles T1 and T2 of peripheral blood lymphocytes in atopic patients&#46;</p><p id="sp0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Methods&#58;</span> We studied 10 atopic patients sensitised to common environmental allergens receiving immunotherapy over one year mean period&#46; Six of these patients were studied before and after immunotherapy&#46; Fourteen atopic patients untreated and 7 non-atopic subjects were used as control groups&#46; Intracellular cytokine production &#40;IFN-&#947;&#59; IL-4&#59; IL-5&#59; IL-10&#41; was determined by flow cytometry following stimulation with phorbol myristate acetate &#40;PMA&#41;&#44; ionomycin and brefeldin&#46; Mann-Whitney U and Wilcoxon non-parametric tests were utilized for the statistical analysis&#46;</p><p id="sp0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Results&#58;</span> The expression of IL-4 and IL-5 in T cells&#44; characteristically increased in atopic patients&#44; respectively 13&#46;8 &#40;3&#46;1 &#8211; 31&#46;8&#41; and 6&#46;7&#37; &#40;1&#46;0 -20&#46;4&#41;&#44; was significantly lower in the immunotherapy group &#91;5&#46;4 &#40;2&#46;9 -15&#46;6&#41; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007 and 2&#46;1&#37; &#40;0&#44;6 &#8211; 4&#46;8&#41; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;035&#93; and similar in the non-atopic control group&#46; The levels of IFN-&#947; did not differ between the studied groups but the ratio IFN-&#947; &#47; IL-4 produced by CD4<span class="elsevierStyleHsp" style=""></span>&#43; T lymphocytes increased significantly in the patients receiving immunotherapy&#46; In addition&#44; there was an increase in the expression of IL-10 by T cells of the immunotherapy group compared to the non-atopic controls &#91;1&#46;9 &#40;1&#46;0 &#8211; 4&#46;9&#41; versus 1&#46;4&#37; &#40;0&#46;9 &#8211; 1&#46;4&#41; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#93;&#44; being more evident in CD8<span class="elsevierStyleHsp" style=""></span>&#43; T lymphocytes&#46; IL-10 correlated significantly with all the profile T2 cytokines &#40;IL-4 and IL-5&#41; and with the phenotype Tc2&#46;</p><p id="sp0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Conclusion&#58;</span> After one year of immunotherapy the peripheral T cells response to a polyclonal stimulation revealed a reduction in IL-4 and IL-5 production&#44; characteristically increased in atopic disease&#46; The increase of IL-10 that we found in our study suggested the existence of a profile T2 regulatory population&#44; more evident in CD8<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T lymphocytes&#46;</p><p id="sp0060" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Rev Port Pneumol 2006&#59; XII &#40;2&#41;&#58; 107-130</span></p></span>"
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Vol. 12. Issue 2.
Pages 107-130 (March - April 2006)
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Vol. 12. Issue 2.
Pages 107-130 (March - April 2006)
Prémio Thomé Villar/Boehringer Ingelheim 2004**

Trabalho vencedor ex-aequo (Secção A)

\Thomé Villar/Boehringer Ingelheim Award 2004*
Open Access
Repercussão da imunoterapia específica na população T1e T2de linfócitos periféricos em doentes atópicos
Specific immunotherapy effect on peripheral blood T1/T2 lymphocytes in atopic patients
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Manuela Rebordão1, Luís Delgado2, Helena Pinto3, Augusto Remédios4, L. Taborda-Barata5
1 Técnica Superior de Saúde. Assistente principal. Serviço de Análises Clínicas do Hospital Militar de Belém/Senior Health Technician. Senior assistant. Belém Military Hospital Analysis Clinic
2 Professor Associadoda Faculdade de Medicina da Universidade do Porto. Serviço e Laboratório de Imunologia, Faculdade de Medicina da Universidade do Porto, Hospital de São João, Porto/Associate Professor at Porto University Medical School. Immunology Unit and Laboratory, Porto University Medical School, Hospital de São João, Porto
3 Tenente-coronel médica – Directora do Serviço de Pneumologia do Hospital Militar de Belém/Medical Lieutenant Colonel – Director of Pulmonology Unit, Belém Military Hospital
4 Tenente-coronel farmacêutico – Director do Serviço de Análises Clínicas do Hospital Militar de Belém/Pharmacist Lieutenant Colonel – Director of Analysis Clinic, Belém Military Hospital
5 Professor Auxiliar de imunologia clínica, Faculdade de Ciências da Saúde, Universidade da Beira Interior. Director do Serviço de Imunoalergologia do Hospital Pêro Covilhã/Assistant Professor Immunology Unit, Beira Interior University Health Sciences School. Immunoallergologist, Director of Immunoallergology Unit, Pêro Covilhã Hospital
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A coordenação das características humorais e celulares da resposta alérgica, sabe-se hoje, está dependente da regulação por linfócitos T. As vacinas de alergénios são uma terapêutica que consegue modular a resposta das células T, e cujos mecanismos imunológicos permanecem incompletamente esclarecidos.

Objectivo: Avaliar o efeito da imunoterapia, após um ano de tratamento, na expressão de citocinas de perfil T1 e T2 em linfócitos de sangue periférico de doentes atópicos.

Material e métodos: Estudaram-se dez doentes atópicos sensibilizados a aeroalergénios comuns a fazerem vacinas de alergénios num período médio de um ano. Dentre estes, seis foram estudados antes e após a vacina. Como controlo estudou-se um grupo atópico sem imunoterapia constituído por 14 doentes também sensibilizados a aeroalergénios comuns e um grupo de indivíduos não atópicos, saudáveis, constituído por 7 elementos. A activação dos linfócitos T fez-se com PMA, ionomicina e brefeldina e estudaram-se as citocinas intracitoplasmáticas IFN-γ, IL-4, IL-5 e IL-10 por citometria de fluxo. Procedeu-se a análise estatística por testes não paramétricos (Teste de Mann-Whitney U e Wilcoxon), considerando-se significativo p0,05.

Resultados: A expressão de IL-4 e IL-5 nas células T, caracteristicamente aumentada nos doentes atópicos, respectivamente 13,8 (3,1-31,8) e 6,7% (1,0-20,4), é significativamente mais baixa no grupo que realizou a imunoterapia [5,4 (2,9-15,6) p=0,007 e 2,1% (0,6-4,8) p=0,035] não diferindo do grupo controlo não atópico [5,1 (4,1-6,9) e 1,0 (0,4-2,1)]. Os níveis de IFN-γ não variaram significativamente entre os três grupos estudados, mas a razão IFN-γ/ /IL-4 nos linfócitos T CD4 aumentou significativamente nos doentes submetidos a imunoterapia. Por outro lado, houve um aumento da expressão de IL-10 nas células T circulantes do grupo sob imunoterapia, comparativamente a controlos não atópicos [1,9 (1,0-4,9) versus 1,4% (0,9-1,4) p=0,02], sendo mais evidente nos linfócitos T CD8. A IL-10 correlacionou-se de forma significativa com todas as citocinas de perfil T2 (IL-4 e IL-5) e com o fenótipo Tc2.

Conclusão: Após um ano de imunoterapia, a resposta das células T do sangue periférico a uma estimulação policlonal evidenciou uma diminuição da expressão das citocinas (IL-4 e IL-5), caracteristicamente aumentadas na doença alérgica. O aumento da IL-10, que também verificámos, sugere a existência de uma população reguladora de perfil T2, sendo mais evidente nos linfócitos T CD8.

Rev Port Pneumol 2006; XII (2): 107-130

Keywords:
Immunotherapy
T1 and T2 lymphocytes
ratio IFN-γ / IL-4
IL-10
Palavras chave:
Imunoterapia
linfócitos T1 e T2
razão IFN-γ / IL-4
IL-10
Abstract

Allergen-specific immunotherapy has been used for successful treatment of atopic diseases. They may act by modifying the patterns of cytokines produced by T cells. However, the precise mechanism by which it accomplishes these effects is still incompletely understood.

Objective: To evaluate the effect of one year immunotherapy on cytokines profiles T1 and T2 of peripheral blood lymphocytes in atopic patients.

Methods: We studied 10 atopic patients sensitised to common environmental allergens receiving immunotherapy over one year mean period. Six of these patients were studied before and after immunotherapy. Fourteen atopic patients untreated and 7 non-atopic subjects were used as control groups. Intracellular cytokine production (IFN-γ; IL-4; IL-5; IL-10) was determined by flow cytometry following stimulation with phorbol myristate acetate (PMA), ionomycin and brefeldin. Mann-Whitney U and Wilcoxon non-parametric tests were utilized for the statistical analysis.

Results: The expression of IL-4 and IL-5 in T cells, characteristically increased in atopic patients, respectively 13.8 (3.1 – 31.8) and 6.7% (1.0 -20.4), was significantly lower in the immunotherapy group [5.4 (2.9 -15.6) p=0.007 and 2.1% (0,6 – 4.8) p=0.035] and similar in the non-atopic control group. The levels of IFN-γ did not differ between the studied groups but the ratio IFN-γ / IL-4 produced by CD4+ T lymphocytes increased significantly in the patients receiving immunotherapy. In addition, there was an increase in the expression of IL-10 by T cells of the immunotherapy group compared to the non-atopic controls [1.9 (1.0 – 4.9) versus 1.4% (0.9 – 1.4) p=0.02], being more evident in CD8+ T lymphocytes. IL-10 correlated significantly with all the profile T2 cytokines (IL-4 and IL-5) and with the phenotype Tc2.

Conclusion: After one year of immunotherapy the peripheral T cells response to a polyclonal stimulation revealed a reduction in IL-4 and IL-5 production, characteristically increased in atopic disease. The increase of IL-10 that we found in our study suggested the existence of a profile T2 regulatory population, more evident in CD8+T lymphocytes.

Rev Port Pneumol 2006; XII (2): 107-130

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