Low-Dose IL-2 Induces Regulatory T Cell-Mediated Control of Experimental Food Allergy.
Regulatory T cells (Tregs) are pivotal for maintenance of immune self-tolerance and also regulate immune responses to exogenous Ags, including allergens. Both decreased Treg number and function have been reported in allergic patients, offering new therapeutic perspectives. We previously demonstrated that Tregs can be selectively expanded and activated by low doses of IL-2 (ld-IL-2) inducing immunoregulation without immunosuppression and established its protective effect in autoimmune diseases. In this study, we evaluated the ability of ld-IL-2 to control allergy in an experimental model of food allergy. Ld-IL-2 induced Treg expansion and activation that elicited protection against clinical manifestations of food allergy in two mouse models with OVA and peanut. This clinical effect was lost in Treg-depleted mice, demonstrating the major contribution of Tregs in ld-IL-2 efficacy. Mechanistic studies further indicated that protection from allergy could be explained by a Treg-dependent local modification of the Th1/Th2 balance and an inhibition of mast cell recruitment and activation. Preventive and therapeutic effects of ld-IL-2 were observed over a 7-mo-period, highlighting its long-term efficacy. This study demonstrated that ld-IL-2 is efficient to prevent and to treat allergic immune responses, and thus represents a promising therapeutic strategy for managing allergic diseases.
Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 6, UMRS 959, I, F-75013 Paris, France; INSERM, UMRS 959, I, F-75013 Paris, France; and Service de Biothérapies et Centre d'Investigation Clinique en Biothérapie, Groupe Hospitalier Pitié Salpêtrière, Assistance Publique - Hôpitaux de Paris, 75013 Paris, France.
Benjamin
0000-0002-9315-0010
B
Bonnet
Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 6, UMRS 959, I, F-75013 Paris, France; INSERM, UMRS 959, I, F-75013 Paris, France; and.
James
0000-0001-8014-5725
J
Vigneron
Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 6, UMRS 959, I, F-75013 Paris, France; INSERM, UMRS 959, I, F-75013 Paris, France; and.
Béatrice
0000-0002-6415-6712
B
Levacher
Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 6, UMRS 959, I, F-75013 Paris, France; INSERM, UMRS 959, I, F-75013 Paris, France; and.
Thomas
0000-0002-4140-498X
T
Vazquez
Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 6, UMRS 959, I, F-75013 Paris, France; INSERM, UMRS 959, I, F-75013 Paris, France; and.
Fabien
0000-0001-9950-4011
F
Pitoiset
Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 6, UMRS 959, I, F-75013 Paris, France; INSERM, UMRS 959, I, F-75013 Paris, France; and.
Faustine
0000-0002-7038-2978
F
Brimaud
Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 6, UMRS 959, I, F-75013 Paris, France; INSERM, UMRS 959, I, F-75013 Paris, France; and Service de Biothérapies et Centre d'Investigation Clinique en Biothérapie, Groupe Hospitalier Pitié Salpêtrière, Assistance Publique - Hôpitaux de Paris, 75013 Paris, France.
Guillaume
0000-0003-1343-752X
G
Churlaud
Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 6, UMRS 959, I, F-75013 Paris, France; INSERM, UMRS 959, I, F-75013 Paris, France; and Service de Biothérapies et Centre d'Investigation Clinique en Biothérapie, Groupe Hospitalier Pitié Salpêtrière, Assistance Publique - Hôpitaux de Paris, 75013 Paris, France.
David
0000-0002-0054-3422
D
Klatzmann
Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 6, UMRS 959, I, F-75013 Paris, France; INSERM, UMRS 959, I, F-75013 Paris, France; and Service de Biothérapies et Centre d'Investigation Clinique en Biothérapie, Groupe Hospitalier Pitié Salpêtrière, Assistance Publique - Hôpitaux de Paris, 75013 Paris, France bertrand.bellier@upmc.fr.
Bertrand
0000-0001-8921-5478
B
Bellier
D000485:Allergens / Q000276:immunology; D000818:Animals; D010367:Arachis / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D007376:Interleukin-2 / Q000627:therapeutic use*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058408:Th1-Th2 Balance
D000485:Allergens; D007376:Interleukin-2; D010047:Ovalbumin