We investigated the effects that mouse interleukin 3 (IL-3), in comparison to mouse IL-2, has on the generation of cytotoxic effectors capable of killing line 1 tumor cells. These potent immunological mediators were delivered locally using gene transfection, rather than systemically, to the tumor site. We created line 1 transfectants that express high levels of IL-3 (3750 units/ml) or IL-2 (200 units/ml) by driving transcription from the β-actin promoter. These levels of expression significantly enhanced tumor rejection in syngeneic mice. Tumor-infiltrating lymphocytes purified from IL-3 or IL-2 transfected tumors showed a dramatically enhanced cytotoxic response to parental line 1 targets. Also, IL-2, but not IL-3, expression enhanced the nonspecific lysis of YAC-1 cells. In vivo depletion of CD8+ cells with monoclonal antibody 2.43 abrogated the generation of cytotoxic effectors in both cases. Interestingly, depletion of CD4+ cells with monoclonal antibody GK1.5 abrogated the IL-3-mediated cytotoxic response but not the IL-2-mediated response. In vivo depletion of CD4+ or CD8+ cells abrogated the effect IL-3 had on reducing tumorigenicity. Reverse polymerase chain reaction analysis demonstrates that IL-3 transfected tumors, when compared to untransfected tumors, express increased levels of IL-2 and IL-4 mRNA. These results strongly suggest that IL-3, unlike IL-2, works to generate cytotoxic effectors by a mechanism that requires CD4+ cells.

1

This work was supported in part by Grant ACS IM493. B. A. P. was supported by NIH Grant T32 AI07285, and A. J. M. was supported in part by NIH Grant T32 GM07356.

2

Manuscript 95 from the Immunology Division.

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