Cutting edge: Tumor-specific CTL are constitutively cross-armed in draining lymph nodes and transiently disseminate to mediate tumor regression following systemic CD40 activation

Philip A. Stumbles, Robyn Himbeck, Jeffrey A Frelinger, Edward J. Collins, Richard A. Lake, Bruce W S Robinson

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51 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5923-5928
Number of pages6
JournalJournal of Immunology
Volume173
Issue number10
StatePublished - Nov 15 2004
Externally publishedYes

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Lymph Nodes
Neoplasms
T-Lymphocytes
Growth

ASJC Scopus subject areas

  • Immunology

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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, Philip A.; Himbeck, Robyn; Frelinger, Jeffrey A; Collins, Edward J.; Lake, Richard A.; Robinson, Bruce W S.

In: Journal of Immunology, Vol. 173, No. 10, 15.11.2004, p. 5923-5928.

Research output: Contribution to journalArticle

Stumbles, Philip A. ; Himbeck, Robyn ; Frelinger, Jeffrey A ; Collins, Edward J. ; Lake, Richard A. ; Robinson, Bruce W S. / Cutting edge : Tumor-specific CTL are constitutively cross-armed in draining lymph nodes and transiently disseminate to mediate tumor regression following systemic CD40 activation. In: Journal of Immunology. 2004 ; Vol. 173, No. 10. pp. 5923-5928.
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