1. Alloantigen-specific T-cell hyporesponsiveness induced by dnIKK2 gene-transfected recipient immature dendritic cells.
- Author
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Fan, Cai-bin, Wang, Yi, Wang, Qing-ping, Du, Ke-lin, Wen, Duan-gai, and Ouyang, Jun
- Subjects
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T cells , *DENDRITIC cells , *ANTIGEN analysis , *DOWNREGULATION , *BONE marrow physiology , *FLOW cytometry , *IMMUNOLOGICAL tolerance - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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