title: Antigen presenting B cells facilitate CD4 T cell cooperation resulting in enhanced generation of effector and memory CD4 T cells.
abstract: We show that the in vivo generation of cytokine-producing CD4 T cells specific for a given major histocompatibility class-II (MHCII)-binding peptide of hen egg lysozyme (HEL) is facilitated when mice are immunized with splenic antigen presenting cells (APC) pulsed with this HEL peptide and another peptide that binds a different MHCII molecule. This enhanced generation of peptide-specific effector CD4 T cells requires that the same splenic APC be pulsed with both peptides. Pulsed B cells, but not pulsed dendritic cells (DCs), can mediate CD4 T cell cooperation, which can be blocked by disrupting OX40-OX40L (CD134-CD252) interactions. In addition, the generation of HEL peptide-specific CD4 T cell memory is greater when mice are primed with B cells pulsed with the two peptides than with B cells pulsed with the HEL- peptide alone. Based on our findings, we suggest CD4 T cell cooperation is important for vaccine design, underlies the phenomenon of "epitope-spreading" seen in autoimmunity, and that the efficacy of B cell-depletion in the treatment of human cell-mediated autoimmune disease is due to the abrogation of the interactions between autoimmune CD4 T cells that facilitates their activation.
authors.affiliation: Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: David R
authors.initials: DR
authors.lastname: Kroeger
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Rudulier
authors.forename: Peter A
authors.initials: PA
authors.lastname: Bretscher
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002478:Cells, Cultured; D002645:Chickens; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology*; D015847:Interleukin-4 / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009113:Muramidase / Q000008:administration & dosage / Q000276:immunology; D053278:OX40 Ligand / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011485:Protein Binding; D053262:Receptors, OX40 / Q000378:metabolism; D013154:Spleen / Q000166:cytology
chemical_list: D016207:Cytokines; D053278:OX40 Ligand; D010455:Peptides; D053262:Receptors, OX40; D015847:Interleukin-4; D010047:Ovalbumin; C421864:hen egg lysozyme; D009113:Muramidase