Abstract:
:Although considerable evidence indicates a role for CD4(+) T lymphocytes (T cells) in airway inflammation, little data exist regarding the mechanisms underlying the induction and regulation of CD4(+) T cell reactivity to lung-specific antigens. To dissect the immunologic and molecular mechanisms of CD4(+) T cell dysregulation, reactivity to a self-antigen expressed in the lung of mice bearing a major histocompatibility complex class-II-restricted T cell receptor specific for this antigen was studied. Transgenic mice developed a progressive interstitial pneumonitis characterized by massive lymphocytic and plasmacytic infiltration of interalveolar septa, a clinical picture closely resembling some of the interstitial lung diseases. Pulmonary inflammation reached a plateau state in older mice with prominent formation of lymphoid follicles but reduced interstitial infiltration. Extensive immunologic characterization of self-reactive CD4(+) T cells isolated from the inflamed lung suggested the induction of regulatory T cells in the site of inflammation. Moreover, inflammation was accompanied by broad changes in the gene expression pattern toward a profile partially resembling that of activated, but strikingly, also that of regulatory CD4(+) T cells. Together our data provide important insights into functional and molecular alterations being associated with the induction and/or regulation of T cell-mediated pulmonary inflammation.
journal_name
Am J Respir Crit Care Medauthors
Bruder D,Westendorf AM,Geffers R,Gruber AD,Gereke M,Enelow RI,Buer Jdoi
10.1164/rccm.200404-464OCkeywords:
subject
Has Abstractpub_date
2004-12-01 00:00:00pages
1145-52issue
11eissn
1073-449Xissn
1535-4970pii
200404-464OCjournal_volume
170pub_type
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