Unexpected effects of viral interleukin-10–secreting dendritic cells in vivo: Preferential inhibition of TH2 responses

Abstract

Viral interleukin (IL)-10 (vIL-10) has been widely described as an immunoregulatory cytokine that does not possess the T-cell costimulatory activities of cellular IL-10; it was therefore believed to be a more potent tolerogenic mediator. The immunosuppressive properties of this cytokine are partly attributed to its capacity to render dendritic cells (DCs) unable to undergo full maturation and to activate T cells. We reported here that myeloid DCs retrovirally transduced with vIL-10 had an impaired production of IL-12 and a decreased expression of MHC class II molecules but had minor defects in costimulatory molecule expression and no alteration on CCR5 and CCR7 expression. In mixed leukocyte reaction, vIL-10–transduced C57BL/6 bm12 (MHC class II mismatch) DCs had a reduced capacity to stimulate C57BL/6 wild-type CD4 + T-cell proliferation. We show that bm12 vIL-10–transduced DC administration in CD8 −/− C57BL/6 mice promoted IFN-γ production, down-regulated TH2-type cytokine production, and did not induce skin graft tolerance. These findings suggest that vIL-10–transduced DC may surprisingly facilitate Th1-type inflammatory responses in vivo.