Protection of CD8+ T cells from activation-induced cell death by IL-18.
Role of IL-18 on proliferation and survival of CD8+ T cells, activated by immobilized anti-CD3 antibody (anti-CD3), was examined. Proliferation and survival of activated T cells, especially 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 approximately 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), particularly IL-18Rbeta chain, in naïve 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 reduction 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.
Li
Wen
W
Laboratory of Host Defenses, Institute for Advanced Medical Sciences and Hyogo College of Medicine, Hyogo, Japan.
Kashiwamura
Shin-Ichiro
S
Ueda
Haruyasu
H
Sekiyama
Atsuo
A
Okamura
Haruki
H
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D016923:Cell Death; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D020382:Interleukin-18 / Q000172:deficiency / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D053724:Receptors, Interleukin-18 / Q000378:metabolism*
D020382:Interleukin-18; D053724:Receptors, Interleukin-18