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-LYMPHOCYTES

Recent studies have reported that APC can present particulate exogenou s Ag in the context of class I MHC to CD8(+) CTL, and our laboratory d emonstrated that IL-3 could enhance CTL generation to exogenous Ag, In this paper, we wished to determine whether presentation of particulat e Ag could be enhanced by IL-3. A T cell hybridoma, B3Z86/90.14(B3Z) r estricted to Ova/K-b, was used as an indicator for presentation of par ticulate Ag with class I MHC. When activated, this hybridoma expresses lacZ, allowing a simple colorimetric measurement of Ag-specific T cel l 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 transfe r 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 p otent CTL response. These observations indicate that use of such cells may provide a new avenue for development of tumor vaccines.