难治性哮喘患者CD4 T淋巴细胞免疫调节网络受损
2019/02/19
摘要
背景： 严重哮喘的免疫发病机制与无效的调节反应有关。对于严重难治性哮喘患者个体的CD4 T细胞描述研究较少。
目的：根据严重哮喘患者对治疗的反应，评估其CD4 T淋巴细胞谱，并与其特应性状态和哮喘发病年龄相关性。
方法：我们评估了19名难治性严重哮喘患者（SAR）、21名控制良好或部分控制的严重哮喘患者（CSA）和23名轻中度哮喘患者（MMA）。从PBMC中获得淋巴细胞，并用流式细胞仪测定该人群中不同分子的表达频率。
结果：我们观察到SAR特应性个体的CD4+IFN-γ+T细胞频率高于CSA。此外，在特应性和早发性哮喘（EOA）中，SAR组CD4+CTLA-4+T细胞的频率低于CSA组。在非特应性和迟发性哮喘（LOA）表型中，我们发现SAR患者CD4+Foxp3+T细胞的频率低于CSA患者。我们还观察到在LOA患者中，SAR组CD4+TGF-β+T细胞的频率比CSA组下降。
结论与临床相关性：我们的数据表明，与特应性及EOA和非特应性及LOA哮喘患者相比，难治性哮喘患者低表达CD4 T细胞的不同调节分子。因此，这些结果可能有助于根据哮喘的表型确定哮喘治疗的新的调控策略。
Impaired immunoregulatory network of the cd4 t lymphocytes in refractory asthma.
Fernandes JS, Araujo MI1, de Almeida TVVS, Andrade LS, Lopes DM, de Mello LM, Carvalho EM, Cruz ÁA, Cardoso LS.
Abstract
BACKGROUND: The immunopathogenesis of severe asthma has been associated with an inefficient regulatory response. There are a few studies about the CD4 T cells profile among individuals with severe asthma refractory to treatment.
OBJECTIVE: To evaluate the CD4 T lymphocyte profile from individuals with severe asthma according to their response to treatment, relating to their atopy status and age of asthma onset.
METHODS: We evaluated nineteen individuals with severe asthma refractory to treatment (SAR), 21 with well-controlled or partly controlled severe asthma (CSA) and 23 with mild to moderate asthma (MMA). Lymphocytes were obtained from PBMC and the frequency of expression of different molecules in this population was assessed using the flow cytometry.
RESULTS: We observed the frequency of CD4+ IFN-γ+ T cells was higher in atopic individuals with SAR than with CSA. In addition, among the atopic and early onset asthma (EOA), the frequency of CD4+ CTLA-4+ T cells was lower in the SAR group than the CSA group. In relation to non-atopic and late onset asthma (LOA) phenotypes, we noted the frequency of CD4+ FoxP3+ T cells was lower in individuals with SAR than with CSA. We also observed among the LOA patients, the frequency of CD4+ TGF-β+ T cells was decreased in SAR group than the in CSA group.
CONCLUSION & CLINICAL RELEVANCE: Our data suggest that refractoriness to treatment in asthma is associated with a lower expression of distinct regulatory molecules by CD4 T cells between those who are atopic and have EOA and those who are non-atopic and have LOA. Thus, these results may contribute to the identification of new regulatory strategies to treat asthma according to their phenotypes.
背景： 严重哮喘的免疫发病机制与无效的调节反应有关。对于严重难治性哮喘患者个体的CD4 T细胞描述研究较少。
目的：根据严重哮喘患者对治疗的反应，评估其CD4 T淋巴细胞谱，并与其特应性状态和哮喘发病年龄相关性。
方法：我们评估了19名难治性严重哮喘患者（SAR）、21名控制良好或部分控制的严重哮喘患者（CSA）和23名轻中度哮喘患者（MMA）。从PBMC中获得淋巴细胞，并用流式细胞仪测定该人群中不同分子的表达频率。
结果：我们观察到SAR特应性个体的CD4+IFN-γ+T细胞频率高于CSA。此外，在特应性和早发性哮喘（EOA）中，SAR组CD4+CTLA-4+T细胞的频率低于CSA组。在非特应性和迟发性哮喘（LOA）表型中，我们发现SAR患者CD4+Foxp3+T细胞的频率低于CSA患者。我们还观察到在LOA患者中，SAR组CD4+TGF-β+T细胞的频率比CSA组下降。
结论与临床相关性：我们的数据表明，与特应性及EOA和非特应性及LOA哮喘患者相比，难治性哮喘患者低表达CD4 T细胞的不同调节分子。因此，这些结果可能有助于根据哮喘的表型确定哮喘治疗的新的调控策略。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Clin Exp Allergy. 2019 Jan 28. doi: 10.1111/cea.13351.)
(Clin Exp Allergy. 2019 Jan 28. doi: 10.1111/cea.13351.)
Impaired immunoregulatory network of the cd4 t lymphocytes in refractory asthma.
Fernandes JS, Araujo MI1, de Almeida TVVS, Andrade LS, Lopes DM, de Mello LM, Carvalho EM, Cruz ÁA, Cardoso LS.
Abstract
BACKGROUND: The immunopathogenesis of severe asthma has been associated with an inefficient regulatory response. There are a few studies about the CD4 T cells profile among individuals with severe asthma refractory to treatment.
OBJECTIVE: To evaluate the CD4 T lymphocyte profile from individuals with severe asthma according to their response to treatment, relating to their atopy status and age of asthma onset.
METHODS: We evaluated nineteen individuals with severe asthma refractory to treatment (SAR), 21 with well-controlled or partly controlled severe asthma (CSA) and 23 with mild to moderate asthma (MMA). Lymphocytes were obtained from PBMC and the frequency of expression of different molecules in this population was assessed using the flow cytometry.
RESULTS: We observed the frequency of CD4+ IFN-γ+ T cells was higher in atopic individuals with SAR than with CSA. In addition, among the atopic and early onset asthma (EOA), the frequency of CD4+ CTLA-4+ T cells was lower in the SAR group than the CSA group. In relation to non-atopic and late onset asthma (LOA) phenotypes, we noted the frequency of CD4+ FoxP3+ T cells was lower in individuals with SAR than with CSA. We also observed among the LOA patients, the frequency of CD4+ TGF-β+ T cells was decreased in SAR group than the in CSA group.
CONCLUSION & CLINICAL RELEVANCE: Our data suggest that refractoriness to treatment in asthma is associated with a lower expression of distinct regulatory molecules by CD4 T cells between those who are atopic and have EOA and those who are non-atopic and have LOA. Thus, these results may contribute to the identification of new regulatory strategies to treat asthma according to their phenotypes.
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