title: Natural killer cell depletion fails to influence initial CD4 T cell commitment in vivo in exogenous antigen-stimulated cytokine and antibody responses.
abstract: The role played by NK- and NK1.1-expressing T cells in CD4 T cell activation and induction of immune responses in vivo is controversial. These effector cells of the innate immune response are hypothesized to play a pivotal role in shaping initial T cell activation, with some groups reporting that classical NK cells are required for optimal Th1-like T cell activation, and others supporting a role for NK1.1+ alphabeta T cells in Th2 generation. Here, we examine the impact of in vivo NK cell depletion on the development of exogenous Ag-specific cytokine and Ab responses using a murine model of human immediate hypersensitivity. OVA-specific immune responses were induced in 1) C57Bl/6 bg/bg and bg/+ mice, 2) BALB/c mice pretreated with anti-asialoGM1 or control Ab, and 3) C57Bl/6 mice depleted of NK1.1-expressing cells by in vivo administration of anti-NK1.1 mAb PK136. Depletion efficacy was assessed by functional assays and flow cytometric analysis. Each of these approaches indicated that depletion of NK cells and NK1.1+ CD4+ T cells fails to alter the Th1:Th2 balance of Ag-driven cytokine synthesis, as indicated by OVA-stimulated cytokine synthesis in primary bulk culture. Similarly, the kinetics and intensity of effector responses such as OVA-specific IgG2a and IgE synthesis were neither increased nor decreased in any of the three models examined. The results argue that NK cells and peripheral NK1.1+ T cells do not play an essential role in shaping the induction of Ag-specific immune responses to soluble exogenous Ags, the most common class of inhalant allergen.
authors.affiliation: Department of Immunology, University of Manitoba, Winnipeg, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: C A
authors.initials: CA
authors.lastname: Ellison
authors.forename: J G
authors.initials: JG
authors.lastname: Gartner
authors.forename: K T
authors.initials: KT
authors.lastname: HayGlass
mesh_terms: D000818:Animals; D000941:Antigens / Q000096:biosynthesis / Q000494:pharmacology*; D000950:Antigens, Ly; D000954:Antigens, Surface; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D005677:G(M1) Ganglioside / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010047:Ovalbumin / Q000276:immunology*; D014176:Protein Biosynthesis; D011506:Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D016207:Cytokines; D007136:Immunoglobulins; C527203:KLRB1 protein, human; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D010047:Ovalbumin