Two phenotypically distinct subsets of spleen dendritic cells in rats exhibit different cytokine production and T cell stimulatory activity.
We recently reported that splenic dendritic cells (DC) in rats can be separated into CD4(+) and CD4(-) subsets and that the CD4(-) subset exhibited a natural cytotoxic activity in vitro against tumor cells. Moreover, a recent report suggests that CD4(-) DC could have tolerogenic properties in vivo. In this study, we have analyzed the phenotype and in vitro T cell stimulatory activity of freshly isolated splenic DC subsets. Unlike the CD4(-) subset, CD4(+) splenic DC expressed CD5, CD90, and signal regulatory protein alpha molecules. Both fresh CD4(-) and CD4(+) DC displayed an immature phenotype, although CD4(+) cells constitutively expressed moderate levels of CD80. The half-life of the CD4(-), but not CD4(+) DC in vitro was extremely short but cells could be rescued from death by CD40 ligand, IL-3, or GM-CSF. The CD4(-) DC produced large amounts of the proinflammatory cytokines IL-12 and TNF-alpha and induced Th1 responses in allogeneic CD4(+) T cells, whereas the CD4(+) DC produced low amounts of IL-12 and no TNF-alpha, but induced Th1 and Th2 responses. As compared with the CD4(+) DC that strongly stimulated the proliferation of purified CD8(+) T cells, the CD4(-) DC exhibited a poor CD8(+) T cell stimulatory capacity that was substantially increased by CD40 stimulation. Therefore, as previously shown in mice and humans, we have identified the existence of a high IL-12-producing DC subset in the rat that induces Th1 responses. The fact that both the CD4(+) and CD4(-) DC subsets produced low amounts of IFN-alpha upon viral infection suggests that they are not related to plasmacytoid DC.
Voisine
Cécile
C
Institut National de la Santé et de la Recherche Médicale, Unité 437, Nantes, France.
Hubert
Francois-Xavier
FX
Trinité
Benjamin
B
Heslan
Michèle
M
Josien
Régis
R
D000818:Animals; D000943:Antigens, Differentiation; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics; D018956:CD5 Antigens / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005434:Flow Cytometry; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D022423:Myeloid Cells / Q000166:cytology; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D021122:Protein Subunits; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000943:Antigens, Differentiation; D015704:CD4 Antigens; D018956:CD5 Antigens; D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D021122:Protein Subunits; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12