Recombinant adenovirus-transduced human dendritic cells engineered to secrete interleukin-10 (IL-10) suppress Th1-type responses while selectively activating IL-10-producing CD4+ T cells.
Recombinant adenoviruses (rAd) are efficient tools for genetic modification of human dendritic cells (DC) in vitro. Infection of DCs by rAd encoding beta-galactosidase (betagal) results in partial maturation of DCs, as witnessed by the upregulation of major histocompatibility complex and costimulatory molecules. Accordingly, these DCs are more potent stimulators of Th1-type proliferative responses. We now demonstrate that infection of immature DCs with rAd encoding human interleukin (IL)-10 results in the secretion by the DCs of large amounts of IL-10, while not affecting expression of activation markers indicative of partial DC maturation. In contrast to rAd-betagal-infected DCs, rAdIL-10-infected DCs are very poor stimulators of monoclonal and polyclonal Th1-type responses. Instead, stimulation of nonpolarized CD4+ T-cell cultures with rAdIL-10-infected DCs selectively activates and expands an IL-10-producing CD4+ T-cell subset capable of suppressing Th1 responses in vitro. Our data argue that rAd-infected human DCs genetically engineered to produce IL-10 may be exploited for the modulation of harmful Th1-type responses in transplantation and autoimmune diseases.
Rea
Delphine
D
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Laface
Drake
D
Hutchins
Beth
B
Kwappenberg
Kitty
K
Melief
Cornelis J M
CJ
Hoeben
Rob C
RC
Offringa
Rienk
R
D000256:Adenoviridae / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D016207:Cytokines; D016753:Interleukin-10