Adjuvant effect of IL-12:: Conversion of peptide antigen administration from tolerizing to immunizing for CD8+ T cells in vivo

CD8(+) T cells from TCR transgenic 2C mice, specific for SIYRYYGL peptide bound to H-2K(b), were adoptively transferred into C57BL/6 recipients to allow monitoring of their location, numbers, and phenotype upon peptide challenge. Recipients were primed by s.c. injection of SIYRYYGL alone or with CFA or IL-12, and the transferred cells then tracked by flow cytometry using the 1B2 mAb specific for the 2C TCR, Peptide alone induced a transient and weak expansion of 1B2(+) cells in the draining lymph nodes (DLN) by day 3, but these cells were tolerant to secondary peptide challenge. In contrast, priming with CFA/peptide resulted in a large clonal expansion of 1B2(+) cells in DLN by day 3, and the cells exhibited a CD25(high)CD44(high) phenotype, blast transformation, and lytic effector function. By day 5, 1B2(+) cell numbers decreased in the DLN and increased in the spleen and blood, 1B2(+) cells with a memory phenotype persisted through day 60 in the DLN, spleen, and blood and responded to secondary peptide challenge. Immunization with peptide, along with IL-12, mimicked the adjuvant effects of CFA with respect to phenotype, clonal expansion, effector function, and establishment of memory, IL-12 was not unique in providing this adjuvant effect. however, since CFA/peptide immunization of IL-12-deficient recipient mice also resulted in 1B2(+) T cell activation and clonal expansion. Thus, CFA or IL-12 can enhance Ag-specific CD8(+) T cell responses to peptide, demonstrating that an inflammatory cytokine(s) can support activation and prevent tolerance induction.