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Publication : Regulation of innate CD8+ T-cell activation mediated by cytokines.

First Author  Freeman BE Year  2012
Journal  Proc Natl Acad Sci U S A Volume  109
Issue  25 Pages  9971-6
PubMed ID  22665806 Mgi Jnum  J:185505
Mgi Id  MGI:5429091 Doi  10.1073/pnas.1203543109
Citation  Freeman BE, et al. (2012) Regulation of innate CD8+ T-cell activation mediated by cytokines. Proc Natl Acad Sci U S A 109(25):9971-6
abstractText  Virus-specific CD8(+) T cells develop the ability to function in an "innate" capacity by responding to a remarkable array of cytokines in a TCR-independent manner. Although several cytokines such as IL-12 and IL-18 have been identified as key regulators of CD8(+) T-cell activation, the role of other cytokines and the ways in which they interact with each other remain unclear. Here, we have used an unbiased, systematic approach to examine the effects of 1,849 cytokine combinations on virus-specific CD8(+) T-cell activation. This study identifies several unexpected cytokine combinations that synergize to induce antigen-independent IFNgamma production and CD69 up-regulation by CD8(+) T cells in addition to cytokines that exhibit differential regulatory functions, with the ability to either enhance or inhibit T-cell IFNgamma production, depending on which cytokine partner is present. These findings underscore the complexity of cytokine interactions while also providing insight into the multifaceted regulatory network controlling virus-specific CD8(+) T-cell functions.
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