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Role of Regulatory T Cells in the Antigen Specific Induction of Tolerance in Murine Asthma.

Natural and inducible regulatory T cells (Tregs) are key players in controlling the development of asthmatic inflammation. To examine the respective role of these subsets in the induction of allergen specific tolerance in established asthma, BALB/c mice were sensitized to OVA and tolerized intranasally with OVA. This led to a marked upregulation of CD4+CD25+Foxp3+ T cells in the lungs, which were regulatory as shown by their suppressive and anergic characteristics in vitro. When mice were depleted of CD25+ T cells using the anti‐CD25 mAb PC61, depletion severely hampered tolerance induction as indicated by a strong recruitment of eosinophils into BALF and a vigorous T cell response to OVA upon challenge, in contrast to non depleted mice. However, in vivo transfer of CD4+CD25+ T cells had no effect on lung inflammation whereas transfer of CD4+CD25− T cells led to reduced eosinophils recruitment upon challenge. PKH26 labeled CD4+CD25− T cells did not proliferate in vivo, although they did proliferate in vitro. When stimulated with OVA in vitro, CD4+CD25− T cells produced high amounts of IL10, low IL‐5 and no TGFβ, IL‐17 or IFNγ. They were equally distributed in the spleen, BLN and lungs. In conclusion, both CD4+CD25+ and CD4+CD25− T cells appear to be essential in tolerance induction. The functional relationship between both subsets will have to be further analyzed.