Both exogenous and endogenous interleukin-10 affects the maturation of bone-marrow-derived dendritic cells in vitro and strongly influences T-cell priming in vivo.
In order to avoid autoimmunity and excessive tissue destruction, the action of certain immunoinhibitory substances are very important for negative regulation of the immune system. Interleukin-10 (IL-10) is an important immunoregulatory cytokine which is thought to negatively affect both T cells and antigen-presenting cells in vivo. Adoptive transfer of IL-10-treated bone-marrow-derived dendritic cells (BMDCs) may be one therapeutic avenue to inhibit autoimmunity. In this study we present a comprehensive analysis of the effects of IL-10 on murine BMDC. We demonstrate that IL-10 can prevent BMDC maturation, as measured by both cytokine production and T-cell priming capacity in vitro. Furthermore, we show that IL-10 can inhibit DC maturation induced by strong stimulatory signals such as lipopolysaccharide or a mixture of cytokines (interferon-gamma, tumour necrosis factor-alpha, IL-4). Interestingly, maturation of both T helper 1- and T helper 2-inducing DCs, characterized by the induction of high levels of interferon-gamma and IL-4-production by responding T cells, respectively, was inhibited by IL-10 in vitro. Finally, our data suggest that both endogenous and exogenous IL-10 affect the T-cell stimulatory capacity of BMDCs after injection of in vitro-treated BMDCs into naïve mice. These data both support existing data as well as point towards a new understanding of the many aspects of IL-10-mediated immunosuppression.
Haase
Claus
C
Hagedorn Research Institute, Gentofte, Denmark. csha@novonordisk.com
Jørgensen
Trine N
TN
Michelsen
Birgitte K
BK
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D016753:Interleukin-10 / Q000276:immunology* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000276:immunology; D053701:Receptors, Interleukin-10; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D008070:Lipopolysaccharides; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10