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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1179-1186.
Prepublished online as a Blood First Edition Paper on October 7, 2004; DOI 10.1182/blood-2004-07-2833.
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Submitted July 22, 2004
Accepted September 21, 2004
Differential regulation of virus-specific T cell effector functions following activation by peptide or innate cytokines
Carol Beadling and Mark K Slifka*
Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA
* Corresponding author; email: slifkam{at}ohsu.edu.
Robust CD8+ T cell activation is vital for the recovery from many viral infections, and is orchestrated via the integration of signals delivered through surface molecules including the T cell antigen receptors (TcR) and cytokine receptors. Little is known about how virus-specific T cells interpret sequential or combined stimulation through these receptors, which must undoubtedly occur in vivo during antiviral immune responses. When measured in real time, peptide antigen and the cytokines, IL-12 and IL-18, independently regulate the on/off kinetics of protective (IFN , TNF ) and immunomodulatory (IL-2, CD40L) cytokine production by activated T cells and memory T cells. The remarkable differences in effector functions elicited by innate or adaptive signals (IL-12/IL-18 or peptide/MHC, respectively) illustrate the complex and stringent regulation of cytokine expression by CD8+ T cells. Together, these results indicate how antiviral T cells incorporate multiple signals from their local microenvironment and tailor their cytokine responses accordingly.

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