Regulation of lung Th 1 and Th 2 CD4+ T cell responses

Wan, Kong-Sang (2001) Regulation of lung Th 1 and Th 2 CD4+ T cell responses. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

A large body of evidence suggests that mucosal T cells orchestrate the inflammatory processes in asthma. However, little is known of how T cell responses in the airways are regulated. To address this issue the DO 11.10 ovalbumin (OVA)- specific T cell receptor transgenic mouse was used to model Thl- and Th2-mediated pulmonary inflammation. Following the adoptive transfer into BALB/c mice, DO 11.10 T cells bearing a Thl or Th2 phenotype entered the lungs of recipient mice. Moreover, the inhalation of an aerosolized solution of OVA resulted in the onset of a pulmonary neutrophila and eosinophilia, respectively. Stimulation of lung mononuclear cells (LMC) with OVA 323-339 peptide induced the production of interferon-γ in Thl-recipients, and IL-4 and IL-5 in Th2-recipient mice. In addition, higher levels of IL-4 and IL-5 were found in the bronchoalveolar fluid (BALF) obtained from Th2 recipient mice that inhaled OVA. Invariably, inhalation of OVA by either Thl or Th2 recipients resulted in the LMC entering a state of growth arrest, since proliferative responses by LMC to antigen were minimal. These data demonstrate that the injected Thl and Th2 DO 11.10 T cells retained their phenotype in vivo folio whig inhalation of OVA aerosols.

Using the DO 11.10 model of pulmonary inflammation the role of cyclooxygenase-2 (COX-2) and COX-2 dependent prostanoids in regulating pulmonary inflammation was examined. High levels of prostaglandins were produced in the airways of both Thl and Th2 recipient mice. Treatment of mice with either indomethacin or lysine-aspirin (inhibitors of both COX-1 and COX-2) dramatically reduced the levels of all the prostaglandins in the BALF.

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