title: OX40 signals during priming on dendritic cells inhibit CD4 T cell proliferation: IL-4 switches off OX40 signals enabling rapid proliferation of Th2 effectors.
abstract: In this study we examined the role and regulation of OX40 signals during CD4 T cell priming on dendritic cells (DCs). Contrary to expectation, OX40-deficient cells proliferated more rapidly than their normal counterparts, particularly when stimulated with peptide in the absence of added cytokines. This proliferative advantage was not apparent for Th2-differentiated cells. When the reasons for this were investigated, we found that the cytokine IL-4 specifically down-regulated expression of OX40 ligand on T, B, and DCs, but not on the CD4(+)CD3(-) cells linked with selection of Th2 cells into the memory compartment. OX40 ligand expression was also down-regulated on rapidly proliferating Th1 effectors. These data are compatible with OX40 signals acting during priming as a check on naive T cell proliferation while T cells integrate additional DC signals. This would serve to limit inappropriate T cell responses. In contrast, OX40 signals from CD4(+)CD3(-) cells located in the outer T zone select proliferating Th2 effectors into the memory T cell pool.
authors.affiliation: Medical Research Council Centre for Immune Regulation, Birmingham Medical School, Birmingham, United Kingdom.
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.forename: Vasilios
authors.initials: V
authors.lastname: Bekiaris
authors.forename: Fiona M
authors.initials: FM
authors.lastname: McConnell
authors.forename: Fabrina M C
authors.initials: FM
authors.lastname: Gaspal
authors.forename: Chandra
authors.initials: C
authors.lastname: Raykundalia
authors.forename: Peter J L
authors.initials: PJ
authors.lastname: Lane
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053278:OX40 Ligand; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D048069:Tumor Necrosis Factors
chemical_list: D017252:CD3 Complex; D006131:Growth Inhibitors; D008024:Ligands; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; D015847:Interleukin-4