TY - JOUR
T1 - Differential regulation of virus-specific T-cell effector functions following activation by peptide or innate cytokines
AU - Beadling, Carol
AU - Slifka, Mark K.
PY - 2005/2/1
Y1 - 2005/2/1
N2 - 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 (TcRs) 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, interleukin 12 (IL-12) and IL-18, independently regulate the on/off kinetics of protective (Interferon γ, tumor necrosis factor α) 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, 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.
AB - 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 (TcRs) 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, interleukin 12 (IL-12) and IL-18, independently regulate the on/off kinetics of protective (Interferon γ, tumor necrosis factor α) 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, 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.
UR - http://www.scopus.com/inward/record.url?scp=12844266709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12844266709&partnerID=8YFLogxK
U2 - 10.1182/blood-2004-07-2833
DO - 10.1182/blood-2004-07-2833
M3 - Article
C2 - 15471952
AN - SCOPUS:12844266709
SN - 0006-4971
VL - 105
SP - 1179
EP - 1186
JO - Blood
JF - Blood
IS - 3
ER -