CD40-deficient Dendritic Cells Producing Interleukin-10, but not Interleukin-12, Induce T-cell Hyporesponsiveness In Vitro and Prevent Acute Allograft Rejection
| Autor: | Gao, J. X., Madrenas, J., Zeng, W., Cameron, M. J., Zhang, Z., Wang, J. J., Zhong, R., Grant, D. |
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| Rok vydání: | 1999 |
| Předmět: |
Graft Rejection
Lipopolysaccharides Male Homologous Cells T-Lymphocytes Inbred C57BL Microbiology Mice Antigens CD40 CD40 Immune Tolerance Animals Transplantation Homologous Antigens Inbred BALB C Cells Cultured Immunology and Infectious Disease Transplantation Mice Inbred BALB C Mice Inbred C3H Cultured Dendritic Cells Flow Cytometry Adoptive Transfer Interleukin-12 Inbred C3H Interleukin-10 Mice Inbred C57BL |
| Zdroj: | Microbiology & Immunology Publications |
| Popis: | The induction of an immune response or tolerance is mediated by corresponding subsets of dendritic cells (DC). However, the property of tolerogenic DC is not clear. Recently, we have characterized a population of CD11c+ splenic DC derived from long-term mixed leucocyte culture (LT-MLC), which are able to proliferate upon stimulation and have a strong primary mixed leucocyte reaction (MLR)-stimulating activity in conventional MLR. In this study, we show that, in contrast to the irradiated ones, non-irradiated LT-MLC-derived DC induce polyclonal antigen-specific T-cell hyporesponsiveness when cocultured with allogeneic splenocytes for 3-11 days. The degree of the hyporesponsiveness increased with the length of coculture. Although these DC expressed major histocompatibility complex class II and B7 costimulatory molecules, which are down-regulated during coculture, they expressed very low or undetectable CD40 before and after coculture, respectively. The CD40-deficient DC spontaneously produce interleukin-10 (IL-10), but not IL-12. The skewed balance between IL-10 and IL-12 is associated with their capability to induce T-cell hyporesponsiveness, because a neutralizing antibody to IL-10, exogenous recombinant IL-12 or lipopolysaccharide (LPS) significantly blocked the hyporesponsiveness. Accordingly, infusion of a small number of non-irradiated LT-MLC-derived DC (5x105) significantly prolonged the survival of a vascularized heterotopic murine heart transplant, whereas irradiated DC accelerated graft rejection. These data suggest that CD40-deficient DC producing IL-10, but not IL-12 can induce T-cell hyporesponsiveness in vitro and in vivo. |
| Databáze: | OpenAIRE |
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