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Clinical implications of CD4+ T cell subsets in adult atopic asthma patients.

ABSTRACT: T cells play a central role in chronic inflammation in asthma. However, the roles of individual subsets of T cells in the pathology of asthma in patients remain to be better understood.We investigated the potential signatures of T cell subset phenotypes in asthma using fresh whole blood from adult atopic asthma patients (n = 43) and non-asthmatic control subjects (n = 22). We further assessed their potential clinical implications by correlating asthma severity.We report four major features of CD4+ T cells in the blood of atopic asthma patients. First, patients had a profound increase of CCR7+ memory CD4+ T cells, but not CCR7- memory CD4+ T cells. Second, an increase in CCR4+ CD4+ T cells in patients was mainly attributed to the increase of CCR7+ memory CD4+ T cells. Accordingly, the frequency of CCR4+CCR7+ memory CD4+ T cells correlated with asthma severity. Current common asthma therapeutics (including corticosteroids) were not able to affect the frequency of CCR4+CCR7+ memory CD4+ T cell subsets. Third, patients had an increase of Tregs, as assessed by measuring CD25, Foxp3, IL-10 and CTLA-4 expression. However, asthma severity was inversely correlated only with the frequency of CTLA-4+ CD4+ T cells. Lastly, patients and control subjects have similar frequencies of CD4+ T cells that express CCR5, CCR6, CXCR3, CXCR5, CD11a, or ?4 integrin. However, the frequency of ?4+ CD4+ T cells in patients correlated with asthma severity.CCR4+CCR7+ memory, but not CCR4+CCR7- memory, ?4+, and CTLA4+ CD4+ T cells in patients show significant clinical implications in atopic asthma. Current common therapeutics cannot alter the frequency of such CD4+ T cell subsets in adult atopic asthma patients.

SUBMITTER: Wiest M

PROVIDER: S-EPMC5833086 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Clinical implications of CD4<sup>+</sup> T cell subsets in adult atopic asthma patients.

Wiest Matthew M Upchurch Katherine K Yin Wenjie W Ellis Jerome J Xue Yaming Y Lanier Bobby B Millard Mark M Joo HyeMee H Oh SangKon S

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 20180302

<h4>Background</h4>T cells play a central role in chronic inflammation in asthma. However, the roles of individual subsets of T cells in the pathology of asthma in patients remain to be better understood.<h4>Methods</h4>We investigated the potential signatures of T cell subset phenotypes in asthma using fresh whole blood from adult atopic asthma patients (n = 43) and non-asthmatic control subjects (n = 22). We further assessed their potential clinical implications by correlating asthma severity. ...[more]

PMID: 29507584

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Project description:BACKGROUND:Perturbations to the composition and function of bronchial bacterial communities appear to contribute to the pathophysiology of asthma. Unraveling the nature and mechanisms of these complex associations will require large longitudinal studies, for which bronchoscopy is poorly suited. Studies of samples obtained by sputum induction and nasopharyngeal brushing or lavage have also reported asthma-associated microbiota characteristics. It remains unknown, however, whether the microbiota detected in these less-invasive sample types reflect the composition of bronchial microbiota in asthma. RESULTS:Bacterial microbiota in paired protected bronchial brushings (BB; n?=?45), induced sputum (IS; n?=?45), oral wash (OW; n?=?45), and nasal brushings (NB; n?=?27) from adults with mild atopic asthma (AA), atopy without asthma (ANA), and healthy controls (HC) were profiled using 16S rRNA gene sequencing. Though microbiota composition varied with sample type (p?<?0.001), compositional similarity was greatest for BB-IS, particularly in AAs and ANAs. The abundance of genera detected in BB correlated with those detected in IS and OW (r median [IQR] 0.869 [0.748-0.942] and 0.822 [0.687-0.909] respectively), but not with those in NB (r?=?0.004 [-?0.003-0.011]). The number of taxa shared between IS-BB and NB-BB was greater in AAs than in HCs (p?<?0.05) and included taxa previously associated with asthma. Of the genera abundant in NB, only Moraxella correlated positively with abundance in BB; specific members of this genus were shared between the two compartments only in AAs. Relative abundance of Moraxella in NB of AAs correlated negatively with that of Corynebacterium but positively with markers of eosinophilic inflammation in the blood and BAL fluid. The genus, Corynebacterium, trended to dominate all NB samples of HCs but only half of AAs (p?=?0.07), in whom abundance of this genus was negatively associated with markers of eosinophilic inflammation. CONCLUSIONS:Induced sputum is superior to nasal brush or oral wash for assessing bronchial microbiota composition in asthmatic adults. Although compositionally similar to the bronchial microbiota, the microbiota in induced sputum are distinct, reflecting enrichment of oral bacteria. Specific bacterial genera are shared between the nasal and the bronchial mucosa which are associated with markers of systemic and bronchial inflammation.

Project description:BackgroundThe circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored.ObjectiveWe sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects.MethodsFlow cytometry was used to measure IFN-γ, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4+/CD8+ T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA)+ versus systemic/CLA- T cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies.ResultsAlthough CLA+ TH1 frequencies were significantly lower in infants with AD versus all older patients (P < .01), frequencies of CLA+ TH2 T cells were similarly expanded across all AD age groups compared with control subjects (P < .05). After infancy, CLA- TH2 frequencies were increased in patients with AD in all age groups, suggesting systemic immune activation with disease chronicity. IL-22 frequencies serially increased from normal levels in infants to highly significant levels in adolescents and adults compared with levels in respective control subjects (P < .01). Unsupervised clustering aligned the AD profiles along an age-related spectrum from infancy to adulthood (eg, inducible costimulator molecule and IL-22).ConclusionsThe adult AD phenotype is achieved only in adulthood. Unique cytokine signatures characterizing individual pediatric endotypes might require age-specific therapies. Future longitudinal studies, comparing the profile of patients with cleared versus persistent pediatric AD, might define age-specific changes that predict AD clearance.

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Clinical implications of CD4+ T cell subsets in adult atopic asthma patients.

Publications

Clinical implications of CD4<sup>+</sup> T cell subsets in adult atopic asthma patients.

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