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IL-3 Enhances Both Presentation of Exogenous Particulate Antigen in Association with Class I Major Histocompatibility Antigen and Generation of Primary Tumor-Specific Cytolytic T Lymphocytes¹

Kun-Yun Yeh^*, Alexander J. McAdam^2,*, Beth A. Pulaski^3,*, Nilabh Shastri, John G. Frelinger^* and Edith M. Lord^4,*

^* Department of Microbiology and Immunology and Cancer Center Immunology Program, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; and Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720

Recent studies have reported that APC can present particulate exogenous Ag in the context of class I MHC to CD8⁺ CTL, and our laboratory demonstrated that IL-3 could enhance CTL generation to exogenous Ag. In this paper, we wished to determine whether presentation of particulate Ag could be enhanced by IL-3. A T cell hybridoma, B3Z86/90.14 (B3Z) restricted to Ova/K^b, was used as an indicator for presentation of particulate Ag with class I MHC. When activated, this hybridoma expresses lacZ, allowing a simple colorimetric measurement of Ag-specific T cell stimulation. We demonstrated that bone marrow cells stimulated by IL-3 in vivo and in vitro exhibited significantly increased presentation of exogenous OVA linked to beads. Lysate from OVA-transfected line 1 murine lung adenocarcinoma cells (line 1/OVA) was also presented by IL-3-stimulated bone marrow cells, suggesting that these APC can process tumor fragments or debris. Studies using TAP1/2-deficient mice and Ag presentation inhibitors indicate that this exogenous Ag presentation is mediated via the conventional class I MHC pathway. Adoptive transfer of IL-3-stimulated bone marrow cells pulsed with lysate from line 1/OVA tumor cells into naive recipient mice led to the generation of a potent CTL response. These observations indicate that use of such cells may provide a new avenue for development of tumor vaccines.

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