title: CD4+CD25+ T cell depletion impairs tolerance induction in a murine model of asthma.
abstract: BACKGROUND
  Regulatory T cells (Tregs) are key players in controlling the development of airway inflammation. However, their role in the mechanisms leading to tolerance in established allergic asthma is unclear.
  
  
  OBJECTIVE
  To examine the role of Tregs in tolerance induction in a murine model of asthma.
  
  
  METHODS
  Ovalbumin (OVA) sensitized asthmatic mice were depleted or not of CD25(+) T cells by anti-CD25 PC61 monoclonal antibody (mAb) before intranasal treatment (INT) with OVA, then challenged with OVA aerosol. To further evaluate the respective regulatory activity of CD4(+)CD25(+) and CD4(+)CD25(-) T cells, both T cell subsets were transferred from tolerized or non-tolerized animals to asthmatic recipients. Bronchoalveolar lavage fluid (BALF), T cell proliferation and cytokine secretion were examined.
  
  
  RESULTS
  Intranasal treatment with OVA led to increased levels of IL-10, TGF-beta and IL-17 in lung homogenates, inhibition of eosinophil recruitment into the BALF and antigen specific T cell hyporesponsiveness. CD4(+)CD25(+)Foxp3(+) T cells were markedly upregulated in lungs and suppressed in vitro and in vivo OVA-specific T cell responses. Depletion of CD25(+) cells before OVA INT severely hampered tolerance induction as indicated by a strong recruitment of eosinophils into BALF and a vigorous T cell response to OVA upon challenge. However, the transfer of CD4(+)CD25(-) T cells not only suppressed antigen specific T cell responsiveness but also significantly reduced eosinophil recruitment as opposed to CD4(+)CD25(+) T cells. As compared with control mice, a significantly higher proportion of CD4(+)CD25(-) T cells from OVA treated mice expressed mTGF-beta.
  
  
  CONCLUSIONS
  Both CD4(+)CD25(+) and CD4(+)CD25(-) T cells appear to be essential to tolerance induction. The relationship between both subsets and the mechanisms of their regulatory activity will have to be further analyzed.
authors.affiliation: Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Boudousquié
authors.forename: C
authors.initials: C
authors.lastname: Pellaton
authors.forename: N
authors.initials: N
authors.lastname: Barbier
authors.forename: F
authors.initials: F
authors.lastname: Spertini
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D018893:Bronchoalveolar Lavage; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007108:Immune Tolerance; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D012333:RNA, Messenger