Signal 3 availability limits the CD8 T cell response to a solid tumor

Julie M. Curtsinger, Michael Y. Gerner, Debra C. Lins, Matthew F. Mescher

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


CD8 T cells need a third signal, along with Ag and costimulation, for effective survival and development of effector functions, and this can be provided by IL-12 or type I IFN. Adoptively transferred OT-I T cells, specific for H-2Kb and OVA, encounter Ag in the draining lymph nodes of mice with the OVA-espressing E.G7 tumor growing at a s.c. site. The OT-I cells respond by undergoing limited clonal expansion and development of effector functions (granzyme B expression and IFN-γ production), and they migrate to the tumor where they persist but fail to control tumor growth. In contrast, OT-I T cells deficient for both the IL-12 and type I IFN receptors expand only transiently and rapidly disappear. These results suggested that some signal 3 cytokine is available, but that it is insufficient to support a CTL response that can control tumor growth. Consistent with this, administration of IL-12 at day 10 of tumor growth resulted in a large and sustained expansion of wild-type OT-I cells with enhanced effector functions, and tumor growth was controlled. This did not occur when the OT-I cells lacked the IL-12 and type I IFN receptors, demonstrating that the therapeutic effect of IL-12 results from direct delivery of signal 3 to the CD8 T cells responding to tumor Ag in the signal 3-deficient environment of the tumor.

Original languageEnglish (US)
Pages (from-to)6752-6760
Number of pages9
JournalJournal of Immunology
Issue number11
StatePublished - Jun 1 2007


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