ORAL TOLERANCE TO DEXTRIN MEDIATED BY SPECIFIC SUPPRESSOR T-CELLS INDUCED IN THE INTESTINAL INTRAEPITHELIUM AND THEm SYSTEMIC MIGRATION

Abstract

Antigens presented to the immune systemthrough the oral route induce antigen specificsecretory IgA and systemic unresponsiveness,termed oral tolerance (aT). We studied theinduction ofaT towards a diet antigen:dextrin (DEX) in rats that underwent proteindeprivation and were further re-fed. Peyer'spatches (PP), mesenteric lymph nodes (MLN)and spleen (Sp) cells from protein re-fed (R)rats mediated hyporesponsiveness after transferinto nai"ve recipient rats. Low numbers ofMLN T cells transferred hyporesponsivenesswhile higher numbers transferred an enhancementof the delayed type hypersensitivity(DTH) reaction. MLN T cells were furtherseparated based on their ability to bind Viciavillosa (VV). MLN VV- T cells, mainly CDS+,mediated hyporesponsiveness and MLN VV+T cells (CD45RC+ CD4- CDS- cells)abrogated the hyporesponsiveness. Moreover,Sp DEX adherent T cells were mainly CDS+.Intestinal intraepitheliallymphocytes (iIELs)mainly CDSa+ y8-TCR+ cells also inhibitedthe DTH response to DEX after transfer. Thepositive DTH response to another carbohydrate(levan) indicates the specificity of thesuppression to dextrin. Therefore, our dataindicate that after oral administration ofDEX, two different populations of T cells weregenerated: one found only in the MLN thatmediated DTH responses and the other onecapable of migrating from the intestinalintraepithelium through PP and MLN to theSp, mediating systemic tolerance.