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CD4(+)CD25(+)Foxp3(+) regulatory T cells are dispensable for controlling CD8(+) T cell-mediatedl lung inflammation

 
: Tosiek, Milena J.; Gruber, Achim D.; Bader, Sophie R.; Mauel, Susanne; Hoymann, Heinz-Gerd; Prettin, Silvia; Tschernig, Thomas; Buer, Jan; Gereke, Marcus; Bruder, Dunja

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The Journal of immunology 186 (2011), Nr.11, S.6106-6118
ISSN: 0022-1767
ISSN: 1048-3233
ISSN: 1047-7381
ISSN: 1550-6606
Englisch
Zeitschriftenaufsatz
Fraunhofer ITEM ()
adoptive transfer; CD antigen; CD8-positive T-Lymphocytes; forkhead transcription factor; immunologic memory; integrin alpha chains; Interleukin-2 receptor alpha subunit; L-Selectin; mice, inbred BALB C; reverse transcriptase polymerase chain reaction; regulatory T-Lymphocytes; flow cytometry; gene expression profiling; immune tolerance; lung; transgenic mouse; oligonucleotide array sequence analysis; pneumonia; respiratory function test

Abstract
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.

: http://publica.fraunhofer.de/dokumente/N-181179.html