Regulatory T Cells in COPD

Sponsor

Groningen Research Institute for Asthma and COPD (Other)

Overall Status

Completed

CT.gov ID

NCT00452764

Collaborator

(none)

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Lymphoid follicles, consisting of T-and B cells, are involved in the chronic inflammatory response in COPD. Foxp3 positive regulatory T cells (Tregs) are present in these follicles and may be involved in the suppression of this chronic inflammatory response.

We hypothesise that a dysfunction of Tregs underlies the development of the inflammatory response in COPD. This could be either due to a decreased presence of Tregs in COPD, or to an altered function of Tregs possibly caused by a decreased HO-1 expression and/or an altered TGFβ regulation.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Behavioral: Withdrawal of medication

Detailed Description

COPD is a leading cause of death worldwide and its morbidity and mortality are still rising.So far, no effective treatment is available To find better treatment methods more insight is needed in the nature/origin of the chronic inflammation that underlies the development of COPD.

The important role of neutrophils, macrophages and cytotoxic T cells is well established in this respect, yet the role of CD4 T cells and B cells has only recently (re)attracted attention. We detected the presence of lymphoid follicles in lung tissue of COPD patients, consisting of B cells surrounded by T cells. Recently, we have found the presence of Foxp3 positive T cells as a component of these lymphoid follicles in COPD. Since Foxp3 is a distinctive marker of regulatory T cells (Tregs), this finding suggests that Tregs are involved in the inflammatory response in COPD.

Tregs are important in controlling immunological tolerance and preventing auto-immune responses by inhibiting T-cell responses. Dysfunction of Tregs can lead to auto-immune diseases, allergy and chronic inflammatory diseases. However, nothing is known so far about their contribution to the chronic inflammatory response in COPD. Recent studies show that, next to direct inhibition by cell-cell contact, the inhibitory effects of Tregs are mediated by heme oxygenase-1 (HO-1) expression and membrane bound TGFβ.

We hypothesise that a dysfunction of regulatory T cells underlies the development of the inflammatory response in COPD. This could be due to a decreased presence of Tregs in COPD, or to an altered function of Tregs. The latter may be due to a decreased HO-1 expression, as we have shown in macrophages of COPD patients compared to those in healthy controls, and/or an altered TGFβ regulation, a cytokine that plays a prime role in COPD.

Study Design

Study Type:

Observational

Anticipated Enrollment :

50 participants

Time Perspective:

Prospective

Official Title:

Phenotype and Number of Regulatory T Cells Present in Peripheral Blood of COPD Patients Versus Healthy Controls

Study Start Date :

Jan 1, 2007

Actual Study Completion Date :

Nov 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

COPD patients

Clinical diagnosed COPD
No allergies
Post-bronchodilator FEV1 < 80% predicted, and post-bronchodilator FEV1/FVC < 70%
No use of (inhaled) corticosteroids in the 6 weeks preceding the study
Age > 40
Smokers and ex- smokers > 10 pack years
Ex-smokers have to have quitted smoking for at least one year
No other major current health problems
Informed consent Healthy controls
No signs of pulmonary disease
No allergies or hyperreactivity
No other major current health problems
FEV1 > 90 % predicted, FEV1/FVC > 70%
Age > 40
Never smokers, i.e. no cigarettes last year, and maximal 5 pack years
Smokers and ex- smokers > 10 pack years
Ex-smokers have to have quitted smoking for at least one year
Informed consent