| First Author | Curtsinger JM | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 11 | Pages | 6752-60 |
| PubMed ID | 17513722 | Mgi Jnum | J:147849 |
| Mgi Id | MGI:3842284 | Doi | 10.4049/jimmunol.178.11.6752 |
| Citation | Curtsinger JM, et al. (2007) Signal 3 availability limits the CD8 T cell response to a solid tumor. J Immunol 178(11):6752-60 |
| abstractText | 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-2K(b) and OVA, encounter Ag in the draining lymph nodes of mice with the OVA-expressing 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-gamma 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. |
