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But, when self-antigen is recognized instead, mechanisms of peripheral tolerance prevent acquisition of effector function to avoid autoimmunity. These distinct responses are influenced by inflammatory and regulatory clues from the tissue environment, but the mechanism(s) by which naive T cells interpret these signals to generate the appropriate immune response are unclear. The identification of the molecules operative in these cell-fate decisions is crucial for developing new treatment options for patients with cancer or autoimmunity, where manipulation of T cell activity is desired to alter the course of disease. With the use of an in vivo murine model to examine CD8+ T cell responses to healthy self-tissue, we correlated self-tolerance with a failure to induce the T-box transcription factors T-bet and Eomes. However, inflammation associated with acute microbial infection induced T-bet and Eomes expression and promoted effector differentiation of self-reactive T cells under conditions that normally favor tolerance. In the context of a Listeria infection, these functional responses relied on elevated T-bet expression, independent of Eomes. Alternatively, infection with LCMV induced higher Eomes expression, which was sufficient in the absence of T-bet to promote effector cytokine production. Our results place T-box transcription factors at a molecular crossroads between CD8+ T cell anergy and effector function upon recognition of peripheral self-antigen, and suggest that inflammation during T cell priming directs these distinct cellular responses.<\/jats:p>","DOI":"10.1189\/jlb.1a0913-500rr","type":"journal-article","created":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T05:07:51Z","timestamp":1400044071000},"page":"397-410","source":"Crossref","is-referenced-by-count":9,"title":["Inflammation programs self-reactive CD8+ T cells to acquire T-box-mediated effector function but does not prevent deletional tolerance"],"prefix":"10.1093","volume":"96","author":[{"given":"Stephanie R","family":"Jackson","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine , St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine , St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa M","family":"Berrien-Elliott","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine , St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Collin L","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine , St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine , St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen J","family":"Donlin","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine , St. Louis, Missouri, USA"},{"name":"Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine , St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan M","family":"Teague","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine , St. Louis, Missouri, USA"},{"name":"St. Louis University Cancer Center , St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,5,13]]},"reference":[{"key":"2023032708475317500_","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.immuni.2005.01.010","article-title":"Peripheral tolerance of CD8 T lymphocytes","volume":"22","author":"Redmond","year":"2005","journal-title":"Immunity"},{"key":"2023032708475317500_","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.immuni.2008.03.012","article-title":"Peripheral CD8+ T cell tolerance to self-proteins is regulated proximally at the T cell receptor","volume":"28","author":"Teague","year":"2008","journal-title":"Immunity"},{"key":"2023032708475317500_","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1084\/jem.20011063","article-title":"CD8(+) T cell tolerance to a tumor-associated antigen is maintained at the level of expansion rather than effector function","volume":"195","author":"Ohlen","year":"2002","journal-title":"J. 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