Protection of CD8 T cells from activation-induced cell death by IL-18

vival of CD8 T cells, activated by immobilized anti-CD3 antibody (anti-CD3), was examined. Pro-liferation and survival of activated T cells, espe-cially that of CD8 T cells, were impaired by IL-18 deficiency [IL-18 knockout (KO)]. After 3 days of culture with anti-CD3, the number of living CD8 T cells from IL-18KO mice was 25 % of that from wild-type (WT) mice but was increased to the same level as WT cells by the addition of IL-18. The expression of IL-18 receptors (IL-18Rs), par-ticularly IL-18R chain, in naı̈ve CD8 T cells was very low but elevated after stimulation with anti-CD3. Blockade of IL-18R by anti-IL-18R antibody on activated WT CD8 T cells resulted in reduc-tion of living cells, suggesting that IL-18 promotes survival of proliferating CD8 T cells. Levels of Bcl-2 in activated IL-18KO CD8 T cells were lower than those in WT cells but were raised by exogenous IL-18. Blockade of IL-18R on WT CD8 T cells decreased the expression of surface markers CD122 and CD94, which are related to cell viability, and the expression of these markers was increased by exogenous IL-18 in IL-18KO cells. These results suggest that IL-18 acts directly on activated CD8 T cells through IL-18Rs and promotes their survival to expand the population