CD4 T Lymphocyte-mediated lung disease: steady state between pathological and tolerogenic immune reactions.
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.
Department of Cell Biology and Immunology, German Research Centre for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany. dbr@gbf.de
Dunja
D
Bruder
Astrid M
AM
Westendorf
Robert
R
Geffers
Achim D
AD
Gruber
Marcus
M
Gereke
Richard I
RI
Enelow
Jan
J
Buer
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D020869:Gene Expression Profiling; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology; D017563:Lung Diseases, Interstitial / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics / Q000276:immunology; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology
D006388:Hemagglutinins; D037721:Pulmonary Surfactant-Associated Protein C