Abstract:
:CD8(+) T cells must detect foreign antigens and differentiate into effector cells to eliminate infections. 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.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Jackson SR,Yuan J,Berrien-Elliott MM,Chen CL,Meyer JM,Donlin MJ,Teague RMdoi
10.1189/jlb.1A0913-500RRsubject
Has Abstractpub_date
2014-09-01 00:00:00pages
397-410issue
3eissn
0741-5400issn
1938-3673pii
jlb.1A0913-500RRjournal_volume
96pub_type
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