Publication Database

CD4 T Lymphocyte-mediated Lung Disease:
Steady State between Pathological and Tolerogenic Immune Reactions (2004)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Bruder, Dunja

Westendorf, Astrid M

Geffers, Robert

Gruber, Achim D (WE 12)

Gereke, Marcus

Enelow, Richard I

Buer, Jan

Quelle

American journal of respiratory and critical care medicine

Bandzählung: 170

Heftzählung: 11

Seiten: 1145 – 1152

ISSN: 0003-0805

Sprache

Englisch

Verweise

Pubmed: 15306530

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.