title: Direct demonstration of CD4 T cell cooperation in the primary in vivo generation of CD4 effector T cells.
abstract: Many observations bear upon the cellular and molecular requirements for CD4 T cell activation. The interaction of CD4 T cells with dendritic cells (DC), central to the induction of most immune responses, is the most studied. However, leukocytes other than DC can dramatically affect the induction and differentiation of CD4 T cells into effector cells. We recently provided indirect evidence that in vivo CD4 T cooperation facilitates the activation of CD4 T cells. Here, we demonstrate that the activation of CD4 T cells, specific for the hen egg lysozyme (HEL)(105)  (-120) peptide, is optimally achieved when BALB/c mice are immunized with additional MHC class II-binding HEL peptides in incomplete Freund's adjuvant. This cooperation cannot be mimicked by the coadministration of LPS or of an agonistic antibody to CD40, at the time of immunization. In contrast, OX40-OX40L interactions are necessary for CD4 T cell cooperation in that an OX40 agonistic antibody can replace, and an OX40L-blocking antibody can abrogate, CD4 T cell cooperation in situations where such cooperation would otherwise enhance the activation of CD4 T cells.
authors.affiliation: Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada.
authors.forename: David R
authors.initials: DR
authors.lastname: Kroeger
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Rudulier
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Peters
authors.forename: Peter A
authors.initials: PA
authors.lastname: Bretscher
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009113:Muramidase / Q000276:immunology; D053278:OX40 Ligand / Q000276:immunology; D053262:Receptors, OX40 / Q000276:immunology
chemical_list: D053278:OX40 Ligand; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; C421864:hen egg lysozyme; D009113:Muramidase