title: T cells are the predominant source of interleukin-5 but not interleukin-4 mRNA expression in the lungs of antigen-challenged allergic mice.
abstract: Pulmonary inflammation is characterized by the accumulation of eosinophils and other leukocytes in the lungs of individuals challenged with antigen. Cytokines released by the Th2 lymphocyte subset, especially interleukin-4 (IL-4) and interleukin-5 (IL-5), are also present and thought to play an important role in this process. Previously, we used a model of aerosolized antigen challenge of sensitized mice to show that T cells were necessary for the accumulation of eosinophils and the production of cytokine steady-state messenger ribonucleic acid (mRNA). T cells were isolated from lung tissue at a time (4 h) when high levels of IL-4 and IL-5 mRNAs had accumulated, and from bronchoalveolar lavage fluid (BALF) and lung tissue at a later time (24 h), when inflammation could be detected by lavage. Lung-derived lymphocytes from sensitized challenged mice consisted of approximately 40% Thyl+ T cells (20% CD4+, 13% CD8+, and 6% CD4+/CD8+) and 30% B220+ B cells. Both BALF- and lung-derived T lymphocytes exhibited a similar activated/memory phenotype (CD44+ CD45RBlo), although lung tissue also contained less differentiated cells (CD44+ CD45RBhi). Thyl+ BALF cells isolated by magnetic bead-mediated separation accounted for approximately 88% of the IL-5 mRNA, 21% of the interferon-gamma (IFN-gamma) mRNA, and < 2% of the IL-4 mRNA detected in unseparated samples by reverse transcriptase-polymerase chain reaction (RT-PCR). Thyl+ T cells from lung tissue accounted for approximately 98% and 89% of IL-5 mRNA, 56% and 80% of IFN-gamma mRNA, and 23% and 40% of IL-4 mRNA at 4 h and 24 h after challenge, respectively. These experiments demonstrate that isolated T cells from BALF and lung are responsible for most of the IL-5 mRNA, but not all of the IFN-gamma or IL-4 mRNAs, detected in this model. These results are consistent with human studies indicating T cells as the major source of IL-5 mRNA in the lungs of asthmatic patients.
authors.affiliation: Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0539, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Garlisi
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: M M
authors.initials: MM
authors.lastname: Billah
authors.forename: R W
authors.initials: RW
authors.lastname: Egan
authors.forename: S P
authors.initials: SP
authors.lastname: Umland
mesh_terms: D000818:Animals; D000941:Antigens / Q000494:pharmacology; D001402:B-Lymphocytes / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015870:Gene Expression / Q000276:immunology; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007156:Immunologic Memory / Q000502:physiology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics*; D015848:Interleukin-5 / Q000235:genetics*; D008168:Lung / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry / Q000502:physiology*; D018800:Thy-1 Antigens / Q000032:analysis
chemical_list: D000941:Antigens; D015848:Interleukin-5; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D015847:Interleukin-4; D007371:Interferon-gamma