Systemic IL -2/Anti -IL-2Ab Complex Combined with Sublingual Immunotherapy Suppresses Experimental Food Allergy through Induction of Mucosal Tolerance

SMALDINI PAOLA LORENA; TREJO FERNANDO; COHEN, JOSE; PIAGGIO, ELIANE; DOCENA GUILLERMO H

Washigton

Congreso; International congress of Mucosal Immunology; 2017

Society for mucosal immunology SMI

&lt;!-- /* Font Definitions */@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-536870145 1073786111 1 0 415 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-AR;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:11.0pt;mso-ansi-font-size:11.0pt;mso-bidi-font-size:11.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-AR;}.MsoPapDefault{mso-style-type:export-only;margin-bottom:10.0pt;line-height:115%;}@page WordSection1{size:8.5in 11.0in;margin:70.85pt 85.05pt 70.85pt 85.05pt;mso-header-margin:35.4pt;mso-footer-margin:35.4pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}--&gt;Cow?s milk allergy(CMA), mediated by an aberrant immunological reaction to cow?s milk proteins(CMP), is one of the most prevalent food allergies in infants and youngchildren worldwide. Oral and sublingual immunotherapies show promise aspotential disease-modifying therapies, although no therapy has yet beenapproved. It has recently been demonstrated that the IL-2/ anti-IL-2 complexselectively expands regulatory T cells (Tregs). We aimed to combine sublingual immunotherapy (SLIT) using lowdoses of the allergen with systemic administration of IL-2/anti-IL2 to improvethe safety and efficacy of the sublingual therapyBalb/c mice weresensitized with CMP and cholera toxin and then treated with PBS (Sens) or CMP(CMPdes) (sublingual) w/wo intraperitoneal injections of IL-2/anti-IL-2(C or CMPdes/C). Mice were orally challenged with CMP and the immuneresponse was in vitro (serum IgE, IL-5 and IFN-γ secretion by splenocytes, lamina propria Tregs, IL-10and TGF-β) and in vivo (clinical score and cutaneous tests) evaluatedWe found a lowermedium clinical score in treated mice after the oral challenge with CMP, ascompared with sensitized mice, with a reduction in skin mast cell reactivity intreated mice, mainly in CMPdes/C group. Immunological changesincluded decreased specific IgE (2,1±0,3OD Sens vs 1,3±0.1CMPdes;1,4±0,9C; 1,1±0,8CMPdes/C), decreased levels of Th2 cytokines andinduction of IL-10 and Tregs in lamina propria of duodenum (14,6±1,2% Sens vs28,0±0,6% CMPdes; 35,2±3,1% C; 42,5±1,8% CMPdes/C) and ofsublingual mucosa of treated mice (p<0,05). The frequency of Tregs in submaxilarand sublingual mucosa was higher in CMPdes/C than CMPdes(p<0,05).However, CMPdes showed an increase of laminapropria tolerogenic dendritic cells CD11c+CD11b-CD8α+(p<0,05)We demonstrated ina murine model of CMA that SLIT down-modulated the mucosal and systemicallergic immune response in sensitized mice and that the IL-2/anti IL-2 compleximproved the sublingual immunotherapy