Alloantigen-specific T-cell hyporesponsiveness induced by dnIKK2 gene-transfected recipient immature dendritic cells
pmid: 26253357
Alloantigen-specific T-cell hyporesponsiveness induced by dnIKK2 gene-transfected recipient immature dendritic cells
Immature dendritic cells (iDCs) have been shown to be able to induce peripheral T-cell tolerance through distinct pathways. Here, we investigated the tolerogenic property of recipient iDCs whose maturation was arrested by a dominant negative mutant of inhibitor of nuclear factor kappa-B kinase 2 (dnIKK2) gene. We found that dnIKK2-iDCs presented a typical semi-mature morphology and expressed lower levels of CD80 and CD86, slightly higher MHC-II than untransfected iDCs. The expression of these molecules had no significant change even dnIKK2-iDCs were pulsed by donor antigen. In primary mixed leukocyte reaction (MLR), dnIKK2-iDCs exhibited impaired ability to stimulate allogeneic T-cells, but induced CD4(+)CD25(-) T-cell formation. In co-culture MLR, these CD4(+)CD25(-) T-cells suppressed T-cell alloreaction in an antigen-specific manner. Besides, CD4(+)CD25(-) T-cells inhibited IL-2 and IFN-γ release, whereas promoted IL-10 and TGF-β secretion. These data suggested recipient dnIKK2-iDCs could maintain peripheral tolerance through down-regulating costimulatory molecule expressions and inducing CD4(+)CD25(-) T-cell formation.
- Shanghai Jiao Tong University China (People's Republic of)
- Soochow University China (People's Republic of)
- The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital) China (People's Republic of)
- First Affiliated Hospital of Soochow University China (People's Republic of)
Male, Isoantigens, T-Lymphocytes, Immunology, Lymphocyte Activation, Transfection, T-Lymphocytes, Regulatory, dnIKK2, Rats, Inbred BN, Immune Tolerance, Animals, Rats, Wistar, Immature dendritic cells, Transplantation, Immune tolerance, Cell Differentiation, Dendritic Cells, I-kappa B Kinase, Rats, Rats, Inbred Lew, Mutation, Cytokines, Lymphocyte Culture Test, Mixed
Male, Isoantigens, T-Lymphocytes, Immunology, Lymphocyte Activation, Transfection, T-Lymphocytes, Regulatory, dnIKK2, Rats, Inbred BN, Immune Tolerance, Animals, Rats, Wistar, Immature dendritic cells, Transplantation, Immune tolerance, Cell Differentiation, Dendritic Cells, I-kappa B Kinase, Rats, Rats, Inbred Lew, Mutation, Cytokines, Lymphocyte Culture Test, Mixed
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