A cross-sectional study in peripheral blood of alphabeta regulatory T cells and T helper 17 cells in emphysema and gammadelta regulatory T cells in exacerbations of COPD
by Nicks, Michael Eugene, Ph.D., UNIVERSITY OF COLORADO HEALTH SCIENCES CENTER, 2011, 89 pages; 3467223

Abstract:

Chronic obstructive pulmonary disease (COPD) is the third most common cause of death in the United States. COPD is defined as a syndrome of smoking related lung disease composed of multiple different phenotypes and immunological pathways that can be present with or without airflow limitation. To identify the role of T cells in these phenotypes, we studied 63 current and former smokers with and without COPD. Subjects were phenotyped by high-resolution computer tomography, spirometry, and clinical data. CD3 αβ and ηδ T regulatory (Treg) cells and T helper cells 17 (Th17) in peripheral blood mononuclear cells (PBMC) were measured by multiple parameter flow cytometry. γδ Treg expressing CD8 were associated with history of exacerbations of COPD (no exacerbation 2494 cells/ml (3563) (median (interquartile range)) and exacerbations 5155 cells/ml (6059) of γδ Treg, p=0.020). γδ Treg cells expressing CD8 were more strongly associated with hospitalization for severe exacerbation of COPD (no severe exacerbations 3203 cells/ml (4185) and severe exacerbations 11572 cells/ml (I20766), p=0.018). Analysis of emphysema was indeterminate for association with any of the following cellular types: αβ Treg cells (identified by FoxP3 transcription factor), and Th17 cells (identified by retinoic orphan receptor γt (RORγt) transcription factor). Expression of immune suppressive cytokines transforming growth factor β (TGFβ) and interluekin 10 (IL-10) from αβ Treg cells and expression of inflammatory cytokines interleukin 17a (IL-17a) from Th17 cells was indeterminate for emphysema as well. However, CD4 IFNγ expressing cells were associated with emphysema (p=0.045) and significantly associated with percent gas trapping in the lungs (p=0.004 and R²=0.149). In secondary analysis, αβ Tregs expressing FoxP3 associated with chronic bronchitis (no chronic bronchitis 10705 cells/ml (9361) and chronic bronchitis 6173 cells/ml (6527), p=0.032) and Th17 cells expressing RORγt associated with percent airway wall thickness (p=0.045 R²=0.054) and Pi10 (p=0.0196 R²=0.079). These results demonstrate γδ Treg cells association with exacerbations, αβ Tregs association with chronic bronchitis, Th17 cells association with airway wall thickness, and CD4IFNγ cells association with percent gas trapping and suggest different immunological basis for different COPD phenotypes.

 
AdviserRussell P. Bowler
SchoolUNIVERSITY OF COLORADO HEALTH SCIENCES CENTER
SourceDAI/B 72-10, p. , Aug 2011
Source TypeDissertation
SubjectsCellular biology; Immunology
Publication Number3467223
Adobe PDF Access the complete dissertation:
 

» Find an electronic copy at your library.
  Use the link below to access a full citation record of this graduate work:
  http://gateway.proquest.com/openurl%3furl_ver=Z39.88-2004%26res_dat=xri:pqdiss%26rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation%26rft_dat=xri:pqdiss:3467223
  If your library subscribes to the ProQuest Dissertations & Theses (PQDT) database, you may be entitled to a free electronic version of this graduate work. If not, you will have the option to purchase one, and access a 24 page preview for free (if available).

About ProQuest Dissertations & Theses
With over 2.3 million records, the ProQuest Dissertations & Theses (PQDT) database is the most comprehensive collection of dissertations and theses in the world. It is the database of record for graduate research.

The database includes citations of graduate works ranging from the first U.S. dissertation, accepted in 1861, to those accepted as recently as last semester. Of the 2.3 million graduate works included in the database, ProQuest offers more than 1.9 million in full text formats. Of those, over 860,000 are available in PDF format. More than 60,000 dissertations and theses are added to the database each year.

If you have questions, please feel free to visit the ProQuest Web site - http://www.proquest.com - or call ProQuest Hotline Customer Support at 1-800-521-3042.