Dataset Information

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy.

ABSTRACT:

Background

The main obstacle to elucidating the role of CD4(+) T cells in allergen-specific immunotherapy (SIT) has been the absence of an adequately sensitive approach to directly characterize rare allergen-specific T cells without introducing substantial phenotypic modifications by means of in vitro amplification.

Objective

We sought to monitor, in physiological conditions, the allergen-specific CD4(+) T cells generated during natural pollen exposure and during allergy vaccination.

Methods

Alder pollen allergy was used as a model for studying seasonal allergies. Allergen-specific CD4(+) T cells were tracked and characterized in 12 subjects with alder pollen allergy, 6 nonallergic subjects, and 9 allergy vaccine-treated subjects by using peptide-MHC class II tetramers.

Results

Allergen-specific CD4(+) T cells were detected in all of the subjects with alder pollen allergy and nonallergic subjects tested. Pathogenic responses--chemoattractant receptor homologous molecule expressed on T(H)2 lymphocytes (CRTH2) expression and T(H)2 cytokine production--are specifically associated with terminally differentiated (CD27(-)) allergen-specific CD4(+) T cells, which dominate in allergic subjects but are absent in nonallergic subjects. In contrast, CD27(+) allergen-specific CD4(+) T cells are present at low frequencies in both allergic and nonallergic subjects and reflect classical features of the protective immune response with high expression of IL-10 and IFN-?. Restoration of a protective response during SIT appears to be due to the preferential deletion of pathogenic (CD27(-)) allergen-specific CD4(+) T cells accompanied by IL-10 induction in surviving CD27(+) allergen-specific CD4(+) T cells.

Conclusions

Differentiation stage divides allergen-specific CD4(+) T cells into 2 distinct subpopulations with unique functional properties and different fates during SIT.

SUBMITTER: Wambre E

PROVIDER: S-EPMC3268867 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy.

Wambre Erik E DeLong Jonathan H JH James Eddie A EA LaFond Rebecca E RE Robinson David D Kwok William W WW

The Journal of allergy and clinical immunology 20111005 2

<h4>Background</h4>The main obstacle to elucidating the role of CD4(+) T cells in allergen-specific immunotherapy (SIT) has been the absence of an adequately sensitive approach to directly characterize rare allergen-specific T cells without introducing substantial phenotypic modifications by means of in vitro amplification.<h4>Objective</h4>We sought to monitor, in physiological conditions, the allergen-specific CD4(+) T cells generated during natural pollen exposure and during allergy vaccinati ...[more]

PMID: 21975176

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Project description:ObjectiveThe study objective was to evaluate the influence of surgeon experience on outcomes in early-stage non-small cell lung cancer.MethodsIn an institutional database, patients undergoing operations for pathologic stage I non-small cell lung cancer were categorized by surgeon experience: within 5 years of completion of training, the low experience group; with 5 to 15 years of experience, the moderate experience group; and with more than 15 years, the high experience group.ResultsFrom 2000 to 2012, 800 operations (638 lobectomies, 162 sublobar resection) were performed with the following distribution: low experience 178 (22.2%), moderate experience 224 (28.0%), and high experience 398 (49.8%). Patients in the groups were similar in age and comorbidities. The use of video-assisted thoracoscopic surgery was higher in the moderate experience group (low experience: 62/178 [34.8%], moderate experience: 151/224 [67.4%], and high experience: 133/398 [33.4%], P < .001), as was the mean number of mediastinal (N2) lymph node stations sampled (low experience: 2.8 ± 1.6, moderate experience: 3.5 ± 1.7, high experience: 2.3 ± 1.4, P < .001). The risk of perioperative morbidity was similar across all groups (low experience: 54/178 [30.3%], moderate experience: 51/224 [22.8%], and high experience: 115/398 [28.9%], P = .163). Five-year overall survival in the moderate experience group was 76.9% compared with 67.5% in the low experience group (P < .001) and 71.4% in the high experience group (P = .006). In a Cox proportional hazard model, increasing age, male gender, prior cancer, and R1 resection were associated with an elevated risk of mortality, whereas being operated on by surgeons with moderate experience and having a greater number of mediastinal (N2) lymph node stations sampled were protective.ConclusionsThe experience of the surgeon does not affect perioperative outcomes after resection for pathologic stage I non-small cell lung cancer. At least moderate experience after fellowship is associated with improved long-term survival.

Dataset Information

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy.

Background

Objective

Methods

Results

Conclusions

Publications

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy.

Similar Datasets

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