tetano
Editor, Senior Moderator
Am J Respir Cell Mol Biol. 2012 Sep 13. [Epub ahead of print]
CD8+ T Cells Responding to Alveolar Self-Antigen Lack CD25 Expression and Fail to Precipitate Autoimmunity.
Tosiek MJ, Bader SR, Gruber AD, Buer J, Gereke M, Bruder D.
Source
Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Abstract
Although the contribution of CD8+ T-cells to the pathogenesis of non-communicable lung diseases has become increasingly appreciated, our knowledge about the mechanisms controlling self-reactive CD8+ T-cells in the respiratory tract remains largely elusive. 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, the outcome of the encounter between pulmonary self-antigen and na?ve CD8+ T-cells in the presence or absence of inflammation was traced after adoptive transfer of fluorescent-labeled CD8+ T-cells specific for the neo-self-antigen influenza A hemagglutinin (HA) into transgenic mice expressing HA specifically in alveolar type II epithelial cells. 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 interleukin-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" while tissue damage after infection or non-infectious 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.
PMID:
22984087
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22984087
CD8+ T Cells Responding to Alveolar Self-Antigen Lack CD25 Expression and Fail to Precipitate Autoimmunity.
Tosiek MJ, Bader SR, Gruber AD, Buer J, Gereke M, Bruder D.
Source
Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Abstract
Although the contribution of CD8+ T-cells to the pathogenesis of non-communicable lung diseases has become increasingly appreciated, our knowledge about the mechanisms controlling self-reactive CD8+ T-cells in the respiratory tract remains largely elusive. 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, the outcome of the encounter between pulmonary self-antigen and na?ve CD8+ T-cells in the presence or absence of inflammation was traced after adoptive transfer of fluorescent-labeled CD8+ T-cells specific for the neo-self-antigen influenza A hemagglutinin (HA) into transgenic mice expressing HA specifically in alveolar type II epithelial cells. 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 interleukin-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" while tissue damage after infection or non-infectious 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.
PMID:
22984087
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22984087