title: The pulmonary environment promotes Th2 cell responses after nasal-pulmonary immunization with antigen alone, but Th1 responses are induced during instances of intense immune stimulation.
abstract: The purpose of this study was to determine the nature of the CD4(+) Th cell responses induced after nasal-pulmonary immunization, especially those coinciding with previously described pulmonary inflammation associated with the use of the mucosal adjuvant, cholera toxin (CT). The major T cell population in the lungs of naive mice was CD4(+), and these cells were shown to be predominantly of Th2 type as in vitro polyclonal stimulation resulted in IL-4, but not IFN-gamma, production. After nasal immunization with influenza Ag alone, Th2 cytokine mRNA (IL-4 and IL-5) levels were increased, whereas there was no change in Th1 cytokine (IL-2 and IFN-gamma) mRNA expression. The use of the mucosal adjuvant, CT, markedly enhanced pulmonary Th2-type responses; however, there was also a Th1 component to the T cell response. Using in vitro Ag stimulation of pulmonary lymphocytes, influenza virus-specific cytokine production correlated with the mRNA cytokine results. Furthermore, there was a large increase in CD4(+) Th cell numbers in lungs after nasal immunization using CT, correlating with the pulmonary inflammatory infiltrate previously described. Coincidentally, both macrophage-inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta mRNA expression increased in the lungs after immunization with Ag plus CT, while only MIP-1beta expression increased when mice were given influenza Ag alone. Our study suggests a mechanism to foster Th1 cell recruitment into the lung, which may impact on pulmonary immune responses. Thus, while Th2 cell responses may be prevalent in modulating mucosal immunity in the lungs, Th1 cell responses contribute to pulmonary defenses during instances of intense immune stimulation.
authors.affiliation: Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: H P
authors.initials: HP
authors.lastname: Jones
authors.forename: L M
authors.initials: LM
authors.lastname: Hodge
authors.forename: K
authors.initials: K
authors.lastname: Fujihashi
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
authors.forename: J R
authors.initials: JR
authors.lastname: McGhee
authors.forename: J W
authors.initials: JW
authors.lastname: Simecka
mesh_terms: D000276:Adjuvants, Immunologic; D000280:Administration, Inhalation; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000096:biosynthesis; D002772:Cholera Toxin / Q000276:immunology; D005260:Female; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008212:Lymphocyte Depletion; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D007252:Influenza Vaccines; D007376:Interleukin-2; D015848:Interleukin-5; D019402:Macrophage Inflammatory Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D002772:Cholera Toxin