Unexpected effects of viral interleukin-10-secreting dendritic cells in vivo: preferential inhibition of TH2 responses.
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-gamma 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.
Moore
F
F
Institute for Medical Immunology, Université Libre de Bruxelles.
Buonocore
S
S
Paulart
F
F
Thielemans
K
K
Goldman
M
M
Flamand
V
V
D000818:Animals; D016827:CD8 Antigens / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D005822:Genetic Vectors; D006085:Graft Survival / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008979:Moloney murine leukemia virus / Q000276:immunology; D012190:Retroviridae / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10