Figure 1.

Dendritic cell–activating versus dendritic cell killing activity of resting and effector CD8⁺ T cells. A, CD8⁺ T cells support IL-12p70 induction in dendritic cell (DC)-CD4⁺ T-cell cocultures. SEA-coated (18, 26) dendritic cells (25) were coincubated with syngeneic CD4⁺ T cells in the absence or presence of (IFNγ-producing, not shown) spleen-isolated CD8⁺ T cells. Soluble IL-4R or IFNγR were used to selectively neutralize IFNγ or IL-4, two cytokines with IL-12–enhancing activities (18, 27, 30). Columns, mean from one experiment of three that yielded similar results; bars, SD. B, interaction with CD8⁺ T cells primes dendritic cells for high IL-12p70 production. Top, dendritic cells were cocultured for 48 h with CD8⁺ T cells from wild-type B6 mice, either in the absence or presence of SEA, before washing and stimulation with CD40L (18, 28). Addition of SEA alone (no T cells) had no or marginal effect (ref. 18 and data not shown). Inset, equivalent effectiveness of naïve and memory CD8⁺ T cells. Bottom, dendritic cells were cocultured with H-2K^b–restricted OVA_257–264–specific CD8⁺ T cells, freshly isolated from spleens of OT-1 mice, in the presence of OVA_257–264 peptide before washing and CD40L stimulation. C, effector T cells kill dendritic cells in vitro. SEA-loaded dendritic cells were cocultured with preactivated (granzyme B^high/CD62L^low; data not shown) effector CD8⁺ T cells from wild-type or perforin-deficient mice. Similar results were obtained in one additional experiment. D, predominance of OVA_257–264/H-2K^b–specific effector versus memory T cells in 1 wk– versus 4 wk–immunized C57BL/6 mice. Note the predominance of tetramer-positive granzyme B⁺/CD62L⁻ effector cells in 1 wk–immunized mice, as opposed to selective presence of granzyme B⁻/CD62L⁺ memory cells in the spleens of 4 wk–immunized mice (n = 3 mice per group; bottom, representative data from individual animals). The frequencies of tetramer-positive CD8⁺ T cells in 1 wk– and 4 wk–immunized mice were 4.3% (±1.5) and 0.7% (±0.3), respectively. Data from one of two experiments that yielded similar results. Inset, selective elimination of OVA_257–264–carrying carboxyfluorescein diacetate succinimidyl ester–labeled dendritic cells in 1 wk–immunized, but not 4 wk–immunized, mice. Naïve mice and 1 wk–preimmunized mice receiving sham-loaded dendritic cells served as control groups. Mice (three per group) were injected with 10⁶ dendritic cells and draining lymph nodes (13, 14) were removed after 16 h.