Essential role for CD103 in the T cell–mediated regulation of experimental colitis

The integrin CD103 is highly expressed at mucosal sites, but its role in mucosal immune regulation remains poorly understood. We have analyzed the functional role of CD103 in intestinal immune regulation using the T cell transfer model of colitis. Our results show no mandatory role for CD103 expression on T cells for either the development or CD4+CD25+ regulatory T (T reg) cell–mediated control of colitis. However, wild-type CD4+CD25+ T cells were unable to prevent colitis in immune-deficient recipients lacking CD103, demonstrating a nonredundant functional role for CD103 on host cells in T reg cell–mediated intestinal immune regulation. Non–T cell expression of CD103 is restricted primarily to CD11chighMHC class IIhigh dendritic cells (DCs). This DC population is present at a high frequency in the gut-associated lymphoid tissue and appears to mediate a distinct functional role. Thus, CD103+ DCs, but not their CD103− counterparts, promoted expression of the gut-homing receptor CCR9 on T cells. Conversely, CD103− DCs promoted the differentiation of IFN-γ–producing T cells. Collectively, these data suggest that CD103+ and CD103− DCs represent functionally distinct subsets and that CD103 expression on DCs influences the balance between effector and regulatory T cell activity in the intestine

CARACTERISATION FONCTIONNELLE DES CELLULES T REGULATRICES

CES DERNIERES ANNEES, LA REGULATION DU NOMBRE DES LYMPHOCYTES PERIPHERIQUES AINSI QUE LES CELLULES T CD4 REGULATRICES CONTROLANT DES REACTIONS IMMUNES AUTOAGRESSIVES ONT ETES L'OBJET DE RECHERCHES INTENSIVES. POUR MIEUX COMPRENDRE L'INTERACTION ENTRE LES CELLULES T CD4 REGULATRICES ET CELLES NON REGULATRICES, DES CELLULES T CD4 CD45RB L O W, CONTENANT DES CELLULES REGULATRICES, ET DES CELLULES T CD4 CD45RB H I G H ONT ETE TRANSFEREES DANS DES RECEVEURS DEFICIENTS RAG-2. ENSUITE, LA RECONSTITUTION PERIPHERIQUE A ETE ETUDIEE LORSQUE LES DEUX POPULATIONS AVAIENT ETE CO-INJECTEES. APRES L'INJECTION, LES CELLULES T CD4 NAIVES MONTRAIENT UNE FORTE CAPACITE DE PROLIFERATION DEPENDANTE DE LA PRESENCE DE CELLULES T CD4 CD45RB L O W. LES CELLULES T CD4 CD45RB L O W PROTEGEAIENT L'HOTE D'UNE MALADIE INDUITE PAR LES CELLULES T CD4 CD45RB H I G H ET MONTRAIENT UN TAUX LIMITE D'EXPANSION. CES RESULTATS ONT MONTRE QUE LES CELLULES T REGULATRICES NATURELLES CONTROLENT LA TAILLE DU COMPARTIMENT CELLULAIRE PERIPHERIQUE T CD4 ACTIVE/MEMOIRE. AFIN DE CARACTERISER EN DETAILS LA REGULATION DU NOMBRE DES LYMPHOCYTES PERIPHERIQUES, LA POPULATION DES CELLULES T CD4 CD45RB L O W A ETE DIVISEE EN UNE SOUS-POPULATION CD25 + ET UNE CD25 . LES CELLULES T CD4 CD25 +, MAIS PAS LES CELLULES CD25 , INHIBAIT L'ACCUMULATION DE CELLULES T CD4 CD45RB H I G H CO-TRANSFEREES. LES CELLULES T CD4 CD25 + PROVENANT DE SOURIS DEFICIENTES EN IL-10 NE PROTEGEAIENT PAS D'UNE MALADIE INFLAMMATOIRE DU COLON. ELLES ACCUMULAIENT UN PLUS GRAND NOMBRE DE CELLULES ET NE POUVAIENT PAS EMPECHER L'EXPANSION DES CELLULES T CD4 CD45RB H I G H. PAR CONSEQUENT, LES CELLULES T CD4 CD25 + DE SOURIS NON MANIPULEES CONTROLAIENT LE NOMBRE DE CELLULES T CD4 PERIPHERIQUES PAR UN MECANISME IMPLIQUANT LA PRODUCTION D'IL-10 PAR DES CELLULES T REGULATRICES. EN CONCLUSION, LES RESULTATS OBTENUS DANS CETTE ETUDE IDENTIFIENT UN NOUVEAU ROLE DES CELLULES T REGULATRICES, LA REGULATION DE LA TAILLE DES POPULATIONS LYMPHOCYTAIRES PERIPHERIQUES, CETTE CAPACITE N'APPARAISSANT QUE DANS LA POPULATION DES CELLULES T CD4 CD25 +.PARIS-BIUSJ-Thèses (751052125) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Intestinal CD103(+), but not CX3CR1(+), antigen sampling cells migrate in lymph and serve classical dendritic cell functions

Chemokine receptor CX3CR1(+) dendritic cells (DCs) have been suggested to sample intestinal antigens by extending transepithelial dendrites into the gut lumen. Other studies identified CD103(+) DCs in the mucosa, which, through their ability to synthesize retinoic acid (RA), appear to be capable of generating typical signatures of intestinal adaptive immune responses. We report that CD103 and CX3CR1 phenotypically and functionally characterize distinct subsets of lamina propria cells. In contrast to CD103(+) DC, CX3CR1(+) cells represent a nonmigratory gut-resident population with slow turnover rates and poor responses to FLT-3L and granulocyte/macrophage colony-stimulating factor. Direct visualization of cells in lymph vessels and flow cytometry of mouse intestinal lymph revealed that CD103(+) DCs, but not CX3CR1-expressing cells, migrate into the gut draining mesenteric lymph nodes (LNs) under steady-state and inflammatory conditions. Moreover, CX3CR1(+) cells displayed poor T cell stimulatory capacity in vitro and in vivo after direct injection of cells into intestinal lymphatics and appeared to be less efficient at generating RA compared with CD103(+) DC. These findings indicate that selectively CD103(+) DCs serve classical DC functions and initiate adaptive immune responses in local LNs, whereas CX3CR1(+) populations might modulate immune responses directly in the mucosa and serve as first line barrier against invading enteropathogens