Regulation of pulmonary T cell responses to inhaled antigen: Role in Th1- and Th2-mediated inflammation

Shiour Ching Lee, Zeina H. Jaffar, Kong Sang Wan, Stephen T. Holgate, Kevan Roberts

Research output: Contribution to journalArticlepeer-review

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-γ. 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.

Original languageEnglish
Pages (from-to)6867-6879
Number of pages13
JournalJournal of Immunology
Volume162
Issue number11
StatePublished - Jun 1 1999

Fingerprint

Dive into the research topics of 'Regulation of pulmonary T cell responses to inhaled antigen: Role in Th1- and Th2-mediated inflammation'. Together they form a unique fingerprint.

Cite this