title: Regulation of pulmonary T cell responses to inhaled antigen: role in Th1- and Th2-mediated inflammation.
abstract: DO11.10 transgenic mice, expressing an OVA-specific TCR, were used to study pulmonary T cell responses to inhaled Ags. Before OVA inhalation, the activation of lung parenchymal T cells elicited both strong proliferative responses and IL-2 production. However, following Ag inhalation the proliferative responses of the lung T cells, when restimulated in vitro with OVA323-339 peptide or immobilized anti-CD3, were severely attenuated and associated with a decrease in the level of production of IL-2 but not IFN-gamma. Such immune regulation was tissue-specific, because T cell responses in the lymph nodes and spleens were normal. This dramatic aerosol-induced attenuation of parenchymal T cell proliferation was also observed in BALB/c mice immunized with OVA and in BALB/c mice following adoptive transfer of DO11.10 T cells bearing either a Th1 or Th2 phenotype. In mice that had received Th2 cells, the reduced proliferative responses were associated with a decrease in IL-2 expression but augmented IL-4 and IL-5 production. Invariably, the inhibition of proliferation was a consequence of the action of F4/80+ interstitial macrophages and did not involve alveolar macrophages or their products. These observations demonstrate that clonal expansion of T cells in the lung compartment is prevented following the onset of either Th1- or Th2-mediated inflammation. This form of immune regulation, which appears as a selective defect in IL-2-driven proliferation, may serve to prevent the development of chronic pulmonary lymphoproliferative responses.
authors.affiliation: University Medicine, Southampton General Hospital, United Kingdom.
authors.forename: S C
authors.initials: SC
authors.lastname: Lee
authors.forename: Z H
authors.initials: ZH
authors.lastname: Jaffar
authors.forename: K S
authors.initials: KS
authors.lastname: Wan
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: K
authors.initials: K
authors.lastname: Roberts
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D000943:Antigens, Differentiation / Q000032:analysis; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002452:Cell Count; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000336:Aerosols; D000941:Antigens; D000943:Antigens, Differentiation; D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D012333:RNA, Messenger; C036763:monocyte-macrophage differentiation antigen; D015847:Interleukin-4; D010047:Ovalbumin