Cutting edge: tumor-specific CTL are constitutively cross-armed in draining lymph nodes and transiently disseminate to mediate tumor regression following systemic CD40 activation
Stumbles, P.A., Himbeck, R., Frelinger, J.A., Collins, E.J., Lake, R.A. and Robinson, B.W.S. (2004) Cutting edge: tumor-specific CTL are constitutively cross-armed in draining lymph nodes and transiently disseminate to mediate tumor regression following systemic CD40 activation. Journal of Immunology, 173 (10). pp. 5923-5928.
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The cross-arming of effector CTL in response to cross-presented tumor Ags is predicted to fail in the absence of CD40 stimulation. However, questions remain regarding the role of CD40 signaling and additional CD4+ T cell-derived signals in this process. To address this, we have analyzed the cross-arming of tumor-specific CTL effectors in vivo in a mouse model of established tumor and tumor regression following CD40 activation. We found that tumor-specific CTL were constitutively cross-armed in tumor-draining lymph nodes during tumor growth and that systemic CD40 activation did not alter CTL cross-arming in the tumor-draining lymph nodes. Rather, CD40 activation induced peripheral dissemination of tumor-specific CTL effectors that required continual CD40 stimulation to maintain peripheral CTL and tumor regression. These data indicate that CD40 activation enhances the peripheral survival of constitutively cross-armed CTL and that persistent CD4+ T cell signals are required for their long-term activity.
|Publication Type:||Journal Article|
|Publisher:||The American Association of Immunologists, Inc.|
|Copyright:||2004 The American Association of Immunologists, Inc.|
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