Intrinsic ability of GM+IL-4 but not Flt3L-induced rat dendritic cells to promote allogeneic T cell hyporesponsiveness.
The influence of GM+IL-4 and Flt3 ligand (FL) on phenotype and function of BM-derived DC from Lewis rats was investigated. GM+IL-4-induced DC, despite expression of CD80/CD86, were less stimulatory than FL-induced DC that expressed low CD80/CD86 and were efficient stimulators of allogeneic T cells. GM+IL-4 DC were CD11b+ OX62lo, whereas FL DC were CD11blo OX62+. Following activation, GM+IL-4 DC produced IL-10 and IL-6, but no IL-12p70, and were resistant to further maturation. FL DC produced IL-12p70, IFN-alpha/beta, IL-10 and IL-6 and underwent maturation. Repeated stimulation of T cells with GM+IL-4 DC inhibited proliferation, cytokine production and induced early T cell apoptosis. FL DC-activated T cells produced large amounts of IFN-gamma/IL-10 and exhibited late T cell apoptosis/necrosis. In vivo, GM+IL-4 DC induced alloAg-specific hyporesponsiveness following T cell restimulation. These results demonstrate that GM+IL-4 DC display intrinsic regulatory properties, inducing passive-cell-death in T cells with potential for inactivation/regulation of alloreactive T cells in transplantation.
Taieb
Aurele
A
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Breitinger
Jeremy J
JJ
Unadkat
Jignesh V
JV
Shufesky
William J
WJ
Morelli
Adrian E
AE
Thomson
Angus W
AW
Lee
W P Andrew
WP
Feili-Hariri
Maryam
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D017690:Cell Transplantation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006649:Histocompatibility Antigens / Q000032:analysis; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007372:Interferons / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology*; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015226:Dinucleoside Phosphates; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006649:Histocompatibility Antigens; D007372:Interferons; D015847:Interleukin-4; D007519:Isoantigens; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C084881:flt3 ligand protein; C015772:CpG dinucleotide