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 b ound to H-2K(b), were adoptively transferred into C57BL/6 recipients to all ow monitoring of their location, numbers, and phenotype upon peptide challe nge. 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 t he 1B2 mAb specific for the 2C TCR, Peptide alone induced a transient and w eak expansion of 1B2(+) cells in the draining lymph nodes (DLN) by day 3, b ut these cells were tolerant to secondary peptide challenge. In contrast, p riming with CFA/peptide resulted in a large clonal expansion of 1B2(+) cell s 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 p eptide, along with IL-12, mimicked the adjuvant effects of CFA with respect to phenotype, clonal expansion, effector function, and establishment of me mory, IL-12 was not unique in providing this adjuvant effect. however, sinc e 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 en hance Ag-specific CD8(+) T cell responses to peptide, demonstrating that an inflammatory cytokine(s) can support activation and prevent tolerance indu ction.