ABSTRACT
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 CD11c(high)MHC class II(high) 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-gamma-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.
Subject(s)
Antigens, CD/immunology , Colitis/immunology , Dendritic Cells/immunology , Immunotherapy/methods , Integrin alpha Chains/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Cell Differentiation/immunology , Colitis/therapy , Cytokines/metabolism , Dendritic Cells/metabolism , Immunity, Mucosal/immunology , Mice , Mice, Knockout , Mice, Mutant Strains , Statistics, Nonparametric , T-Lymphocytes, Regulatory/metabolismSubject(s)
Colitis/etiology , Interleukin-10/physiology , T-Lymphocytes/immunology , Adoptive Transfer , Animals , Colitis/immunology , Colitis/therapy , Humans , Immunosuppression Therapy , Inflammatory Bowel Diseases/etiology , Inflammatory Bowel Diseases/immunology , Interleukin-10/pharmacology , Mice , Recombinant Proteins/pharmacology , T-Lymphocytes/transplantationABSTRACT
Regulatory CD4 T cells with the capacity to inhibit potentially harmful immune responses have been described in various experimental systems. Although the observations are converging towards the naturally activated CD25(+) CD4 T cells as a major population responsible for this protection, there is still considerable disagreement on the molecular and cellular requirements involved to achieve a stable immune homeostasis in vivo.
