Alloantigen-specific T-cell hyporesponsiveness induced by dnIKK2 gene-transfected recipient immature dendritic cells

作者：Fan, Cai-bin; Wang, Yi; Wang, Qing-ping; Du, Ke-lin; Wen, Duan-gai; Ouyang, Jun^*

来源：Cellular Immunology, 2015, 297(2): 100-107.

DOI：10.1016/j.cellimm.2015.07.004

• Immature dendritic cells
• dnIKK2
• Immune tolerance
• Transplantation

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-gamma release, whereas promoted IL-10 and TGF-beta secretion. These data suggested recipient dnIKK2-iDCs could maintain peripheral tolerance through down-regulating costimulatory molecule expressions and inducing CD4(+)CD25(-) T-cell formation.

• 出版日期2015-10
• 单位上海交通大学; 苏州大学