title: CD8(+) T cells responding to alveolar self-antigen lack CD25 expression and fail to precipitate autoimmunity.
abstract: 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.
authors.affiliation: Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Milena J
authors.initials: MJ
authors.lastname: Tosiek
authors.forename: Sophie R
authors.initials: SR
authors.lastname: Bader
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.forename: Marcus
authors.initials: M
authors.lastname: Gereke
authors.forename: Dunja
authors.initials: D
authors.lastname: Bruder
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology / Q000637:transplantation; D002454:Cell Differentiation; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D018836:Inflammation Mediators / Q000378:metabolism; D007376:Interleukin-2 / Q000502:physiology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D001324:Autoantigens; D018836:Inflammation Mediators; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit