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Contribution of regulatory T cells to alleviation of experimental allergic asthma after specific immunotherapy

H Maazi, S Shirinbak, Monique Willart UGent, Hamida Hammad UGent, M Cabanski, L Boon, V Ganesh, AM Baru, G Hansen and Bart Lambrecht UGent, et al. (2012) CLINICAL AND EXPERIMENTAL ALLERGY. 42(10). p.1519-1528
abstract
Background Allergen-specific immunotherapy (SIT) has been used since 1911, yet its mechanism of action remains to be elucidated. There is evidence indicating that CD4+FOXP3+ regulatory T cells (Treg cells) are induced during SIT in allergic patients. However, the contribution of these cells to SIT has not been evaluated in vivo. Objective To evaluate the in vivo contribution of (i) CD4+ CD25+ T cells during SIT and of (ii) SIT-generated inducible FOXP3+ Treg cells during allergen exposure to SIT-mediated suppression of asthmatic manifestations. Methods We used a mouse model of SIT based on the classical OVA-driven experimental asthma. Treg cells were quantified by flow cytometry 24 and 96h post SIT treatment. We depleted CD4+CD25+ T cells prior to SIT, and CD4+FOXP3+ T cells prior to allergen challenges to study their contribution to the suppression of allergic manifestations by SIT treatment. Results Our data show that depletion of CD4+CD25+ T cells at the time of SIT treatment reverses the suppression of airway hyperresponsiveness (AHR), but not of airway eosinophilia and specific IgE levels in serum. Interestingly, the number of CD4+CD25+FOXP3+ T cells is transiently increased after SIT in the spleen and blood, suggesting the generation of inducible and presumably allergen-specific Treg cells during treatment. Depletion of CD4+FOXP3+ Treg cells after SIT treatment partially reverses the SIT-induced suppression of airway eosinophilia, but not of AHR and serum levels of specific IgE. Conclusion and clinical relevance We conclude that SIT-mediated tolerance induction towards AHR requires CD4+CD25+ T cells at the time of allergen injections. In addition, SIT generates CD4+CD25+FOXP3+ T cells that contribute to the suppression of airway eosinophilia upon allergen challenges. Therefore, enhancing Treg cell number or their activity during and after SIT could be of clinical relevance to improve the therapeutic effects of SIT.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
IgE, Hyper-reactivity, asthma, eosinophil, allergen immunotherapy, FOXP3, regulatory T cells, GRASS-POLLEN IMMUNOTHERAPY, TGF-BETA, SUBLINGUAL IMMUNOTHERAPY, TOLERANCE INDUCTION, VENOM IMMUNOTHERAPY, AIRWAY INFLAMMATION, CD4(+)CD25(+) CELLS, DENDRITIC CELLS, MURINE MODEL, MOUSE MODEL
journal title
CLINICAL AND EXPERIMENTAL ALLERGY
Clin. Exp. Allergy
volume
42
issue
10
pages
1519 - 1528
Web of Science type
Article
Web of Science id
000309069200011
JCR category
ALLERGY
JCR impact factor
4.789 (2012)
JCR rank
4/23 (2012)
JCR quartile
1 (2012)
ISSN
0954-7894
DOI
10.1111/j.1365-2222.2012.04064.x
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
3041796
handle
http://hdl.handle.net/1854/LU-3041796
date created
2012-11-05 09:28:02
date last changed
2012-11-05 15:28:25
@article{3041796,
  abstract     = {Background Allergen-specific immunotherapy (SIT) has been used since 1911, yet its mechanism of action remains to be elucidated. There is evidence indicating that CD4+FOXP3+ regulatory T cells (Treg cells) are induced during SIT in allergic patients. However, the contribution of these cells to SIT has not been evaluated in vivo. Objective To evaluate the in vivo contribution of (i) CD4+ CD25+ T cells during SIT and of (ii) SIT-generated inducible FOXP3+ Treg cells during allergen exposure to SIT-mediated suppression of asthmatic manifestations. Methods We used a mouse model of SIT based on the classical OVA-driven experimental asthma. Treg cells were quantified by flow cytometry 24 and 96h post SIT treatment. We depleted CD4+CD25+ T cells prior to SIT, and CD4+FOXP3+ T cells prior to allergen challenges to study their contribution to the suppression of allergic manifestations by SIT treatment. Results Our data show that depletion of CD4+CD25+ T cells at the time of SIT treatment reverses the suppression of airway hyperresponsiveness (AHR), but not of airway eosinophilia and specific IgE levels in serum. Interestingly, the number of CD4+CD25+FOXP3+ T cells is transiently increased after SIT in the spleen and blood, suggesting the generation of inducible and presumably allergen-specific Treg cells during treatment. Depletion of CD4+FOXP3+ Treg cells after SIT treatment partially reverses the SIT-induced suppression of airway eosinophilia, but not of AHR and serum levels of specific IgE. Conclusion and clinical relevance We conclude that SIT-mediated tolerance induction towards AHR requires CD4+CD25+ T cells at the time of allergen injections. In addition, SIT generates CD4+CD25+FOXP3+ T cells that contribute to the suppression of airway eosinophilia upon allergen challenges. Therefore, enhancing Treg cell number or their activity during and after SIT could be of clinical relevance to improve the therapeutic effects of SIT.},
  author       = {Maazi, H and Shirinbak, S and Willart, Monique and Hammad, Hamida and Cabanski, M and Boon, L and Ganesh, V and Baru, AM and Hansen, G and Lambrecht, Bart and Sparwasser, T and Nawijn, MC and van Oosterhout, AJM},
  issn         = {0954-7894},
  journal      = {CLINICAL AND EXPERIMENTAL ALLERGY},
  keyword      = {IgE,Hyper-reactivity,asthma,eosinophil,allergen immunotherapy,FOXP3,regulatory T cells,GRASS-POLLEN IMMUNOTHERAPY,TGF-BETA,SUBLINGUAL IMMUNOTHERAPY,TOLERANCE INDUCTION,VENOM IMMUNOTHERAPY,AIRWAY INFLAMMATION,CD4(+)CD25(+) CELLS,DENDRITIC CELLS,MURINE MODEL,MOUSE MODEL},
  language     = {eng},
  number       = {10},
  pages        = {1519--1528},
  title        = {Contribution of regulatory T cells to alleviation of experimental allergic asthma after specific immunotherapy},
  url          = {http://dx.doi.org/10.1111/j.1365-2222.2012.04064.x},
  volume       = {42},
  year         = {2012},
}

Chicago
Maazi, H, S Shirinbak, Monique Willart, Hamida Hammad, M Cabanski, L Boon, V Ganesh, et al. 2012. “Contribution of Regulatory T Cells to Alleviation of Experimental Allergic Asthma After Specific Immunotherapy.” Clinical and Experimental Allergy 42 (10): 1519–1528.
APA
Maazi, H., Shirinbak, S., Willart, M., Hammad, H., Cabanski, M., Boon, L., Ganesh, V., et al. (2012). Contribution of regulatory T cells to alleviation of experimental allergic asthma after specific immunotherapy. CLINICAL AND EXPERIMENTAL ALLERGY, 42(10), 1519–1528.
Vancouver
1.
Maazi H, Shirinbak S, Willart M, Hammad H, Cabanski M, Boon L, et al. Contribution of regulatory T cells to alleviation of experimental allergic asthma after specific immunotherapy. CLINICAL AND EXPERIMENTAL ALLERGY. 2012;42(10):1519–28.
MLA
Maazi, H, S Shirinbak, Monique Willart, et al. “Contribution of Regulatory T Cells to Alleviation of Experimental Allergic Asthma After Specific Immunotherapy.” CLINICAL AND EXPERIMENTAL ALLERGY 42.10 (2012): 1519–1528. Print.