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Epit Prevents from the Induction of Anaphylaxis to Further Allergens: Role of Naive Tregs
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Lucie Mondoulet, PhD, Vincent Dioszeghy, PhD, Emilie Puteaux, Mélanie Ligouis, Véronique Dhelft, Camille Plaquet, Christophe Dupont, MD PhD, Pierre-Henri Benhamou, MD
Rationale: In milk-sensitized mice, epicutaneous immunotherapy (EPIT) prevents from the induction of anaphylaxis to further allergens via a regulatory T cells (Tregs) mechanism. This study is an in-depth investigation of the Tregs subpopulations involved in this protection.

Methods:

After milk sensitization, mice were treated by EPIT or Sham. CD4+CD25+T cells were isolated from spleen and transferred into not sensitized mice (recipient) following injection of an IL2 blocking antibody. Recipient mice were submitted to a peanut-sensitization procedure and intravenously challenged with peanut.

In a second experiment, Tregs were isolated upon the CD62L+ surface marker defining a naive Tregs population. Naive and effector Tregs were adoptively transferred into recipient mice, which were then submitted to peanut- sensitization and IV challenge. Outcome tools were drop in rectal temperature, hypersensitivity reactions and blood mouse mast cell protease-1 (mMCP1).

Results:

The adoptive transfer of milk EPIT-induced Tregs to recipient mice protected them from sensitization to peanut and from the induction of anaphylaxis (p<0.01). The injection of anti-IL2 before Tregs transfer abrogated the protection from anaphylaxis. Noticeably, the induction by EPIT of naive Tregs also decreased in the presence of anti-IL2. The transfer of naive Tregs seemed to prevent from the drop in temperature after IV challenge (p<0.001) whereas effector Tregs did not confer this protection.

Conclusions:

The protection against sensitization to further allergens observed after EPIT appears to be conferred by the naive Treg fraction.