Immunology 2002 Dec;107(4):489-99
Haase C, Jorgensen TN, Michelsen BK.
Hagedorn Research Institute, Gentofte, Denmark.
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 naive mice.
These data both support existing data as well as point towards a new understanding of the many aspects of IL-10-mediated immunosuppression.