Fachbereich Veterinärmedizin



    CD4+CD25+Foxp3+ Regulatory T Cells are Dispensable for Controlling CD8+ T Cell-mediated Lung Inflammation (2011)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Tosiek, Milena J
    Gruber, Achim D
    Bader, Sophie R
    Mauel, Susanne
    Hoymann, Heinz-Gerd
    Prettin, Silvia
    Tschernig, Thomas
    Buer, Jan
    Gereke, Marcus
    Bruder, Dunja
    Journal of immunology; 186(11) — S. 6106–6118
    ISSN: 0022-1767
    DOI: 10.4049/jimmunol.1000632
    Pubmed: 21518973
    Institut für Tierpathologie

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    Abstract / Zusammenfassung

    Every person harbors a population of potentially self-reactive lymphocytes controlled by tightly balanced tolerance mechanisms. Failures in this balance evoke immune activation and autoimmunity. In this study, we investigated the contribution of self-reactive CD8(+) T lymphocytes to chronic pulmonary inflammation and a possible role for naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells (nTregs) in counterbalancing this process. Using a transgenic murine model for autoimmune-mediated lung disease, we demonstrated that despite pulmonary inflammation, lung-specific CD8(+) T cells can reside quiescently in close proximity to self-antigen. Whereas self-reactive CD8(+) T cells in the inflamed lung and lung-draining lymph nodes downregulated the expression of effector molecules, those located in the spleen appeared to be partly Ag-experienced and displayed a memory-like phenotype. Because ex vivo-reisolated self-reactive CD8(+) T cells were very well capable of responding to the Ag in vitro, we investigated a possible contribution of nTregs to the immune control over autoaggressive CD8(+) T cells in the lung. Notably, CD8(+) T cell tolerance established in the lung depends only partially on the function of nTregs, because self-reactive CD8(+) T cells underwent only biased activation and did not acquire effector function after nTreg depletion. However, although transient ablation of nTregs did not expand the population of self-reactive CD8(+) T cells or exacerbate the disease, it provoked rapid accumulation of activated CD103(+)CD62L(lo) Tregs in bronchial lymph nodes, a finding suggesting an adaptive phenotypic switch in the nTreg population that acts in concert with other yet-undefined mechanisms to prevent the detrimental activation of self-reactive CD8(+) T cells.