title: Comparison of OX40 ligand and CD70 in the promotion of CD4+ T cell responses.
abstract: The TNF superfamily members CD70 and OX40 ligand (OX40L) were reported to be important for CD4(+) T cell expansion and differentiation. However, the relative contribution of these costimulatory signals in driving CD4(+) T cell responses has not been addressed. In this study, we found that OX40L is a more important determinant than CD70 of the primary CD4(+) T cell response to multiple immunization regimens. Despite the ability of a combined TLR and CD40 agonist (TLR/CD40) stimulus to provoke appreciable expression of CD70 and OX40L on CD8(+) dendritic cells, resulting CD4(+) T cell responses were substantially reduced by Ab blockade of OX40L and, to a lesser degree, CD70. In contrast, the CD8(+) T cell responses to combined TLR/CD40 immunization were exclusively dependent on CD70. These requirements for CD4(+) and CD8(+) T cell activation were not limited to the use of combined TLR/CD40 immunization, because vaccinia virus challenge elicited primarily OX40L-dependent CD4 responses and exclusively CD70-dependent CD8(+) T cell responses. Attenuation of CD4(+) T cell priming induced by OX40L blockade was independent of signaling through the IL-12R, but it was reduced further by coblockade of CD70. Thus, costimulation by CD70 or OX40L seems to be necessary for primary CD4(+) T cell responses to multiple forms of immunization, and each may make independent contributions to CD4(+) T cell priming.
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver, Denver, CO 80206, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Kurche
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Burchill
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Sanchez
authors.forename: Catherine
authors.initials: C
authors.lastname: Haluszczak
authors.forename: Ross M
authors.initials: RM
authors.lastname: Kedl
mesh_terms: D000818:Animals; D053282:CD27 Ligand / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007114:Immunization / Q000379:methods; D008089:Listeria monocytogenes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053278:OX40 Ligand / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D053282:CD27 Ligand; D019013:CD40 Antigens; D053278:OX40 Ligand; D051193:Toll-Like Receptors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7