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T-cells in COPD to help or harm? A study of T-cells in COPD patients and related aspects of T-cell function in vitro

Glader, Pernilla LU (2006)
Abstract
Chronic obstructive pulmonary disease, COPD, is manifested by chronic airflow limitation due to inflammation and tissue destruction in the lungs. COPD is caused primarily by smoking and with increasing cigarette consumption in the world, the prevalence for COPD will most probably increase in the future. The chronic inflammation in the lungs of these patients is thought to drive the pathogenesis forward. Neutrophils, macrophages, T-cells and epithelial cells are considered major players in the inflammation. This thesis focuses on T-cells and the occurrence of T-cell populations in BAL, blood and peripheral lung tissue from COPD patients. In addition, T-cell responses to smoke and costimulatory factors were studied in vitro.

... (More)
Chronic obstructive pulmonary disease, COPD, is manifested by chronic airflow limitation due to inflammation and tissue destruction in the lungs. COPD is caused primarily by smoking and with increasing cigarette consumption in the world, the prevalence for COPD will most probably increase in the future. The chronic inflammation in the lungs of these patients is thought to drive the pathogenesis forward. Neutrophils, macrophages, T-cells and epithelial cells are considered major players in the inflammation. This thesis focuses on T-cells and the occurrence of T-cell populations in BAL, blood and peripheral lung tissue from COPD patients. In addition, T-cell responses to smoke and costimulatory factors were studied in vitro.



In the papers covered in this thesis we show that T-cells in BAL displayed a memory phenotype (CD45R0+) and the majority of the cells also expressed the integrin alphaEbeta7, which implies that these cells have previously been situated in the airway epithelium as intraepithelial T-cells. In vitro studies of T-cells from peripheral blood, negative for alphaEbeta7, showed that expression of alphaEbeta7 was increased after exposure to TGF-beta and stimulation of T-cells via LFA-1. In peripheral lung tissue CD4+ and CD8+ T-cells were located at different sites. CD8+ T-cells were more abundant in the epithelium and CD4+T-cells were numerous in lymphoid aggregates found in the parenchyma. The number of lymphoid aggregates found per cm2 tissue tended to be higher in COPD patients than in smokers and never-smokers and constituted of a B-cell core surrounded by T-cells of mainly CD4+ phenotype. In blood the number of CD4+ T-cells was elevated in smokers and CD69 expression on CD4+ T-cells in current smokers correlated with FEV1 percent of predicted, which suggests that high numbers of CD69+CD4+ T-cells in blood of smokers could protect against lung function deterioration while exposure of cigarette smoke is present. Despite high numbers of T-cells present in the lungs of smokers and COPD patients, the lower airways of these patients are often colonized by bacteria. In the present study T-cells exposed to an aqueous cigarette smoke extract were studied with the hypothesis that T-cell functions may be impaired in response to substances in cigarette smoke. Indeed, T-cell activation, proliferation and production of cytotoxic granules were decreased in response to cigarette smoke extract. These data suggest that T-cell defence against airway infections might be impaired in smokers. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Patienter med kroniskt obstruktiv lungsjukdom, KOL, har en försämrad lungfunktion och lider av bronkit och andnöd. Dessa symptom beror troligtvis på en ständigt pågående inflammation i lungan som dels leder till ökad slemproduktion och förträngning av luftrören, dels till emfysem dvs. nedbrytning av lungvävnaden vilket försämrar gasutbytet i lungan. Cigarrettrökning är den största riskfaktorn vid KOL och rökavvänjning är i dag det bästa sättet för KOL patienter att stoppa utvecklingen av sjukdomen. Forskning pågår för att förstå orsakerna till inflammationen vid KOL. Flera celler i immunförsvaret tros vara inblandade i den inflammatoriska processen däribland T-celler. Detta är celler som normalt... (More)
Popular Abstract in Swedish

Patienter med kroniskt obstruktiv lungsjukdom, KOL, har en försämrad lungfunktion och lider av bronkit och andnöd. Dessa symptom beror troligtvis på en ständigt pågående inflammation i lungan som dels leder till ökad slemproduktion och förträngning av luftrören, dels till emfysem dvs. nedbrytning av lungvävnaden vilket försämrar gasutbytet i lungan. Cigarrettrökning är den största riskfaktorn vid KOL och rökavvänjning är i dag det bästa sättet för KOL patienter att stoppa utvecklingen av sjukdomen. Forskning pågår för att förstå orsakerna till inflammationen vid KOL. Flera celler i immunförsvaret tros vara inblandade i den inflammatoriska processen däribland T-celler. Detta är celler som normalt skyddar kroppen mot infektioner och oönskade cellförändringar. De har förmågan att signalera till andra celler i immunförsvaret och kan även själva motarbeta skador och infektioner.



Denna avhandling syftar till att studera närvaron av olika typer av T-celler i lungan och blodet hos KOL patienter, rökare och icke-rökare och till att vidare studera T-cellers respons då de utsätts för cigarettrök. Resultaten från studierna i lunga visade att aggregat av T-celler, med ännu okänd funktion, är vanliga hos KOL patienter. Dessa aggregat kan vara ett resultat av deposition av partiklar från cigarettrök eller ett sätt att försvara lungan mot infektioner som är vanligt förekommande hos KOL patienter. Ett ökat antal s.k. cytotoxiska (CD8+) T-celler påvisades i luftvägsslemhinnan hos rökare och KOL patienter. Denna typ av T-celler har förmågan att driva virusinfekterade värdceller i apoptos, självinducerad celldöd, och har därför föreslagits vara involverade i nedbrytning av lungvävnad. Resultat från studien på blod visade att T-cellers aktivitet i blodet eventuellt kan påverka utvecklingen av KOL. Rökare med många aktiverade s.k. hjälpar (CD4+) T-celler i blodet hade en bättre lungfunktion än rökare med färre celler av denna typ. Resultat från T-cellskulturer odlade i laboratorium visade att ämnen från cigarettrök försämrade T-cellers förmåga att aktiveras, tillväxa och producera de proteiner som T-cellerna använder i försvaret mot virus. Dessa resultat tyder på att cigarrettrökning kan försämra försvaret mot infektioner, vilket kan få stora konsekvenser för KOL patienter som ofta drabbas av akuta försämringsperioder i samband med luftvägsinfektioner. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Dr. Sköld, Magnus, Dept. of Medicine, Karolinska hospital, Stockholm Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Andningsorganen, Respiratory system, Immunologi, serologi, T-cell, inflammation, mucosal immunology, transplantation, serology, Immunology, lymphocyte, chronic obstructive pulmonary disease
pages
118 pages
publisher
Respiratory Medicine and Allergology, Lund University
defense location
Lecture hall 1, Blocket, Lund University hospital
defense date
2006-01-27 13:00:00
ISBN
91-85481-33-5
language
English
LU publication?
yes
additional info
Pernilla Glader, Sebastian Möller, Johanna Lilja, Elisabet Wieslander, Claes-Göran Löfdahl and Karin von Wachenfeldt. . Cigarette smoke extract modulates respiratory defence mechanisms through effects on T-cells and airway epithelial cells Respiratory Medicine, Elsevier (accepted)
Pernilla Glader, Karin von Wachenfeldt and Claes-Göran Löfdahl. . Systemic CD4+ T-cell activation is correlated with FEV1 in smokers Respiratory Medicine, Elsevier (accepted)
Pernilla Glader, Claes-Göran Löfdahl, Karin von Wachenfeldt and Jonas Erjefält. . Distribution of lymphocytes and lymphoid aggregates in peripheral lung tissue from COPD patients (manuscript)
Pernilla Glader, Claes-Göran Löfdahl and Karin von Wachenfeldt. 2005. alphaEbeta7 expression on CD8+ T-cells in COPD BAL fluid and on TGF-beta stimulated T-cells in vitro Lung, vol 183 pp 123-138. Springer Science+Business Media, Inc
id
c1db7ed7-c5f0-40ae-b43d-aa5ac9c2a515 (old id 546083)
date added to LUP
2016-04-01 15:46:06
date last changed
2018-11-21 20:36:13
@phdthesis{c1db7ed7-c5f0-40ae-b43d-aa5ac9c2a515,
  abstract     = {{Chronic obstructive pulmonary disease, COPD, is manifested by chronic airflow limitation due to inflammation and tissue destruction in the lungs. COPD is caused primarily by smoking and with increasing cigarette consumption in the world, the prevalence for COPD will most probably increase in the future. The chronic inflammation in the lungs of these patients is thought to drive the pathogenesis forward. Neutrophils, macrophages, T-cells and epithelial cells are considered major players in the inflammation. This thesis focuses on T-cells and the occurrence of T-cell populations in BAL, blood and peripheral lung tissue from COPD patients. In addition, T-cell responses to smoke and costimulatory factors were studied in vitro.<br/><br>
<br/><br>
In the papers covered in this thesis we show that T-cells in BAL displayed a memory phenotype (CD45R0+) and the majority of the cells also expressed the integrin alphaEbeta7, which implies that these cells have previously been situated in the airway epithelium as intraepithelial T-cells. In vitro studies of T-cells from peripheral blood, negative for alphaEbeta7, showed that expression of alphaEbeta7 was increased after exposure to TGF-beta and stimulation of T-cells via LFA-1. In peripheral lung tissue CD4+ and CD8+ T-cells were located at different sites. CD8+ T-cells were more abundant in the epithelium and CD4+T-cells were numerous in lymphoid aggregates found in the parenchyma. The number of lymphoid aggregates found per cm2 tissue tended to be higher in COPD patients than in smokers and never-smokers and constituted of a B-cell core surrounded by T-cells of mainly CD4+ phenotype. In blood the number of CD4+ T-cells was elevated in smokers and CD69 expression on CD4+ T-cells in current smokers correlated with FEV1 percent of predicted, which suggests that high numbers of CD69+CD4+ T-cells in blood of smokers could protect against lung function deterioration while exposure of cigarette smoke is present. Despite high numbers of T-cells present in the lungs of smokers and COPD patients, the lower airways of these patients are often colonized by bacteria. In the present study T-cells exposed to an aqueous cigarette smoke extract were studied with the hypothesis that T-cell functions may be impaired in response to substances in cigarette smoke. Indeed, T-cell activation, proliferation and production of cytotoxic granules were decreased in response to cigarette smoke extract. These data suggest that T-cell defence against airway infections might be impaired in smokers.}},
  author       = {{Glader, Pernilla}},
  isbn         = {{91-85481-33-5}},
  keywords     = {{Andningsorganen; Respiratory system; Immunologi; serologi; T-cell; inflammation; mucosal immunology; transplantation; serology; Immunology; lymphocyte; chronic obstructive pulmonary disease}},
  language     = {{eng}},
  publisher    = {{Respiratory Medicine and Allergology, Lund University}},
  school       = {{Lund University}},
  title        = {{T-cells in COPD to help or harm? A study of T-cells in COPD patients and related aspects of T-cell function in vitro}},
  url          = {{https://lup.lub.lu.se/search/files/4466018/546084.pdf}},
  year         = {{2006}},
}