Enhanced expression of Fas ligand (CD95L) on T cells after segmental allergen provocation in asthma

Krug, Norbert; Tschernig, Thomas; Balke, Kerstin; Erpenbeck, Veit J.; Meyer, Lars; Bode, Ulrike; Hohlfeld, Jens M.; Pabst, Reinhard; Fabel, H

doi:10.1016/s0091-6749(99)70238-1

Cited by 17 publications

(19 citation statements)

References 21 publications

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“…After effective treatments, such as corticosteroids, increased apoptosis of T-cells and eosinophils was observed in asthmatic subjects [16]. Additionally, T-cells from asthmatics failed to undergo the normal degree of apoptosis following Fas receptor ligation [17], although these cells express the same levels of Fas and Fas ligand as nonasthmatic controls [19]. Taken together, these observations suggested that resistance of T-cells and eosinophils to apoptosis may play a role in maintaining ongoing T-cell activation in asthma.…”

Section: Discussionmentioning

confidence: 99%

Cyclosporin A, apoptosis of BAL T‐cells and expression of Bcl‐2 inasthmatics

Sun¹,

Khan²,

Meng³

et al. 2003

Eur Respir J

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The late asthmatic reaction is characterised by elevated numbers of interleukin‐4/interleukin‐5/CD4‐positive T‐helper cells type 2 in bronchoalveolar lavage fluid (BALF). Cyclosporin A (CsA) is known to inhibit T‐cell proliferation, induce apoptosis of CD4‐positive T‐cells and downregulate cytokine gene expression.It was assessed whether CsA‐induced inhibition of the late asthmatic reaction was associated with apoptosis of BALF T‐lymphocytes and other cell types, as well as expression of the antiapoptotic protein B‐cell leukaemia/lymphoma 2 gene product (Bcl‐2). BALF cells were obtained from asthmatics at baseline and 24 h after allergen-inhalation challenge following prior administration of CsA (n=13) or placebo (n=11).The number of apoptotic CD3‐positive T‐lymphocytes increased in the CsA but not the placebo group. The numbers of Bcl‐2‐positive cells were significantly reduced in the CsA but not the placebo group. The majority of Bcl‐2‐positive cells were CD3‐positive T‐lymphocytes.The beneficial effect of cyclosporin A in asthma may be related to its inhibitory effect on the late asthmatic reactionviainduction of T‐cell apoptosis and decreased B‐cell leukaemia/lymphoma 2 gene product levels.

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Section: Discussionmentioning

confidence: 99%

Cyclosporin A, apoptosis of BAL T‐cells and expression of Bcl‐2 inasthmatics

Sun¹,

Khan²,

Meng³

et al. 2003

Eur Respir J

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“…The regulation of apoptosis could be another factor influencing lymphocyte numbers. In healthy humans over 80% of the BAL T cells carry the Fas antigen (CD95) (33,34), which is involved in cellular mechanisms of apoptosis. In asthmatics, but not in healthy volunteers, the physiological ligand of CD95, Fas ligand (CD95L), is increased on T cells after segmental allergen challenge (34), which suggests increased apoptosis of lymphocytes in the BAL in asthmatics.…”

Section: Discussionmentioning

confidence: 99%

“…In healthy humans over 80% of the BAL T cells carry the Fas antigen (CD95) (33,34), which is involved in cellular mechanisms of apoptosis. In asthmatics, but not in healthy volunteers, the physiological ligand of CD95, Fas ligand (CD95L), is increased on T cells after segmental allergen challenge (34), which suggests increased apoptosis of lymphocytes in the BAL in asthmatics. In a mouse model of lung inflammation increased apoptosis of BAL lymphocytes was also found after intratracheal instillation of sheep erythrocytes (35).…”

Section: Discussionmentioning

confidence: 99%

Lymphocytes Migrate from the Blood into the Bronchoalveolar Lavage and Lung Parenchyma in the Asthma Model of the Brown Norway Rat

Schuster

Tschernig

Krug

et al. 2000

Am J Respir Crit Care Med

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Lymphocyte migration from the blood into the lung has been suggested as being responsible for the increase of lymphocytes, in particular CD4 T cells, in the bronchoalveolar lavage (BAL) and bronchial mucosa in human asthma, but so far there has been no direct proof. We studied lymphocyte immigration and lymphocyte subpopulations in three lung compartments in ovalbumin (OVA)-sensitized and -challenged brown Norway (BN) rats. Increased numbers of CD4 and interleukin 2 (IL-2) receptor-positive T cells were found in the BAL and lung parenchyma in treated animals, but also increased numbers of CD8 T cells, B cells, and natural killer (NK) cells. For direct proof of lymphocyte migration from the blood into the lung, leukocytes were labeled with a fluorescent dye, 5- (and 6-) carboxyfluorescein-diacetate-succinimidyl-ester (CFSE), and injected intravenously immediately prior to OVA aerosol challenge. One day after challenge the number of CFSE(+), i.e., newly immigrated lymphocytes, was determined by flow cytometry gated on the lymphocyte cluster. A 15 times (1.5 times) higher number of CFSE(+) lymphocytes was found in the BAL (the lung parenchyma) of treated animals in comparison with control rats. In the BAL 51.8% of CFSE(+) cells were CD4-positive (parenchyma 72.7%) and 29.4% IL-2 receptor-positive (parenchyma 34.2%). There was no difference whether the leukocytes for labeling and injection were obtained from untreated or from OVA-sensitized donor animals. Our data show that lymphocyte immigration is at least in part responsible for the increase in lymphocyte numbers in the BAL and lung parenchyma in this animal asthma model.

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“…This hypothesis supports several studies in which it has been reported that cells engaged in the inflammatory asthmatic process are less apoptotic. decreased expression of Fas receptor or Fas ligand [6] in asthmatic subjects while other studies have reported an increased expression of Fas receptor and Fas ligand in asthmatic subjects [37,38]. Another study showed that T-cells from asthmatic subjects failed to undergo apotosis following Fas receptor ligation, although these cells express the same levels of Fas and Fas ligand as in nonasthmatic subjects [7].…”

Section: Discussionmentioning

confidence: 99%

Altered apoptosis in bronchoalveolar lavage lymphocytes after allergen exposure of atopic asthmatic subjects

Müller¹,

Grünewald²,

Höglund³

et al. 2006

Eur Respir J

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The increased number of lymphocytes in airways during an asthmatic response is believed to be the result of increased recruitment of these cells. However, it is possible that a decreased apoptotic rate could also contribute to the increased number. The aim of the present study was to investigate whether allergen airway provocation influences the apoptotic phenotype of lung and peripheral blood lymphocytes (PBL) in subjects with atopic asthma.Bronchoalveolar lavage (BAL) lymphocytes and PBL from 12 asthmatic subjects previously challenged with allergen (n57) or saline (n55) were exposed to the apoptotic stimulus tributyltin (TBT) in vitro and assayed for apoptosis.Airway allergen provocation resulted in decreased sensitivity of BAL lymphocytes to TBTinduced apoptosis, with 42.2% (range 33.9-62.5%) apoptotic cells before challenge versus 23.5% (range 15.3-42.4%) after challenge, while PBL were unaffected. The increased apoptosis resistance correlated with higher numbers of Bcl-2-expressing lymphocytes. Interestingly, baseline caspase-3-like activity was significantly elevated in viable BAL lymphocytes compared with viable PBL, and was unaltered by allergen exposure.In conclusion, allergen inhalation renders bronchoalveolar lavage lymphocytes more resistant to apoptosis while peripheral blood lymphocytes were not influenced at all, indicating that the apoptotic phenotype of airway lymphocytes may play a role in asthmatic inflammation.

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Enhanced expression of Fas ligand (CD95L) on T cells after segmental allergen provocation in asthma

Cited by 17 publications

References 21 publications

Cyclosporin A, apoptosis of BAL T‐cells and expression of Bcl‐2 inasthmatics

Cyclosporin A, apoptosis of BAL T‐cells and expression of Bcl‐2 inasthmatics

Lymphocytes Migrate from the Blood into the Bronchoalveolar Lavage and Lung Parenchyma in the Asthma Model of the Brown Norway Rat

Altered apoptosis in bronchoalveolar lavage lymphocytes after allergen exposure of atopic asthmatic subjects

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