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Blood, 5 March 2009, Vol. 113, No. 10, pp. 2256-2264. Prepublished online as a Blood First Edition Paper on October 23, 2008; DOI 10.1182/blood-2008-03-148809. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-03-148809v1 113/10/2256    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Quigley, M. Articles by Yang, Y. Search for Related Content PubMed PubMed Citation Articles by Quigley, M. Articles by Yang, Y. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 31, 2008 Accepted October 13, 2008 A critical role for direct TLR2-MyD88 signaling in CD8 T cell clonal expansion and memory formation following vaccinia viral infection Michael Quigley, Jennifer Martinez, Xiaopei Huang, and Yiping Yang* Departments of Medicine and Immunology, Duke University Medical Center, Durham, NC, United States * Corresponding author; email: yang0029{at}mc.duke.edu. Recent advances have suggested a crucial role of the innate immunity in shaping adaptive immune responses. How activation of innate immunity promotes adaptive T cell responses to pathogens in vivo is not fully understood. It has been thought that TLR-mediated control of adaptive T cell responses is mainly achieved by the engagement of TLRs on APCs to promote their maturation and function. In this study, we showed that direct TLR2-MyD88 signaling in CD8 T cells was also required for their efficient clonal expansion by promoting the survival of activated T cells upon vaccinia viral infection in vivo. Effector CD8 T cells that lacked direct TLR2-MyD88 signaling did not survive the contraction phase to differentiate into long-lived memory cells. Furthermore, we observed that direct TLR2 ligation on CD8 T cells promoted CD8 T cell proliferation and survival in vitro in a manner dependent on PI3K-Akt pathway activation, and that activation of Akt controlled memory cell formation in vivo. These results identify a critical role for intrinsic TLR2-MyD88 signaling and PI3K-Akt pathway activation in CD8 T cell clonal expansion and memory formation in vivo and could lead to the development of new vaccine approaches. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Zhao, C. De Trez, R. Flynn, C. F. Ware, M. Croft, and S. Salek-Ardakani The Adaptor Molecule MyD88 Directly Promotes CD8 T Cell Responses to Vaccinia Virus J. Immunol., May 15, 2009; 182(10): 6278 - 6286. [Abstract] [Full Text] [PDF]

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