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    CD8(+) T Cells Responding to Alveolar Self-Antigen Lack CD25 Expression and Fail to Precipitate Autoimmunity (2012)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Tosiek, Milena J
    Bader, Sophie R
    Gruber, Achim D
    Buer, Jan
    Gereke, Marcus
    Bruder, Dunja
    Quelle
    American journal of respiratory cell and molecular biology; 47(6) — S. 869–878
    ISSN: 1535-4989
    Sprache
    Englisch
    Verweise
    DOI: 10.1165/rcmb.2011-0387OC
    Pubmed: 22984087
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    +49 30 838 62450

    Abstract / Zusammenfassung

    Although the contribution of CD8(+) T cells to the pathogenesis of noncommunicable lung diseases has become increasingly appreciated, our knowledge about the mechanisms controlling self-reactive CD8(+) T cells in the respiratory tract remains largely elusive. The outcome of the encounter between pulmonary self-antigen and naive CD8(+) T cells, in the presence or absence of inflammation, was traced after adoptive transfer of fluorescence-labeled CD8(+) T cells specific for the neo-self-antigen influenza A hemagglutinin into transgenic mice expressing hemagglutinin specifically in alveolar type II epithelial cells in order: to study the outcome of alveolar antigen encounter in the steady state and under inflammatory conditions; to define the phenotype and fate of CD8(+) T cells primed in the respiratory tract; and, finally, to correlate these findings with the onset of autoimmunity in the lung. We found that CD8(+) T cells remain ignorant in the steady state, whereas transient proliferation of self-reactive CD8(+) T cells is induced by forced maturation or licensing of dendritic cells, increases in the antigenic threshold, and targeted release of alveolar self-antigen by epithelial injury. However, these cells fail to acquire effector functions, lack the expression of the high-affinity IL-2 receptor CD25, and do not precipitate autoimmunity in the lung. We conclude that inadvertent activation of CD8(+) T cells in the lung is prevented in the absence of "danger signals," whereas tissue damage after infection or noninfectious inflammation creates an environment that allows the priming of previously ignorant T cells. Failure in effector cell differentiation after abortive priming, however, precludes the establishment of self-perpetuating autoimmunity in the lung.