title: CD4 T cell cooperation is required for the in vivo activation of CD4 T cells.
abstract: We address here the role of CD4 T cell cooperation in the activation of CD4 T cells. Administration of aggregated hen egg lysozyme (HEL) without microbial adjuvant to BALB/c mice normally generates cytokine-producing CD4 T cells specific for the HEL major peptide, HEL(105-120), as well as CD4 T cells specific for HEL non-major peptides. The prior administration of HEL(105-120) ablates the generation of cytokine-secreting CD4 T cells specific for HEL(105-120), as well as the CD4 T cells specific for HEL non-major peptides, normally generated upon HEL challenge. Thus, the activation of HEL non-major peptide-specific CD4 T cells appears to depend upon the HEL(105-120)-specific CD4 T cell population. In contrast, when HEL(105-120) and saline-treated mice are challenged with HEL coupled to ovalbumin (OVA), CD4 T cell responses to HEL non-major peptides and to OVA are the same, whereas treated mice still do not generate cytokine-secreting cells specific for HEL(105-120). We infer that the administration of HEL(105-120) does not generate regulatory cells capable of down-regulating CD4 T cell responses to HEL and OVA peptides. OVA-specific CD4 T cells restore the generation of HEL non-major peptide-specific T cells in the absence of HEL major peptide-specific T cells. We conclude that the generation of CD4 T cells producing IL-2, IFN-gamma and IL-4 requires CD4 T cell cooperation and that this cooperation is not mediated simply by CD40-CD40L interactions. We also conclude from these observations that there is no requirement for a microbial or danger signal for CD4 T cell activation.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatchewan, Canada. NPeters@niaid.nih.gov
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Peters
authors.forename: David R
authors.initials: DR
authors.lastname: Kroeger
authors.forename: Steven
authors.initials: S
authors.lastname: Mickelwright
authors.forename: Peter A
authors.initials: PA
authors.lastname: Bretscher
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009113:Muramidase / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D007376:Interleukin-2; D010455:Peptides; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; C421864:hen egg lysozyme; D009113:Muramidase