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Protection of CD8+ T cells from activation‐induced cell death by IL‐18
Author(s) -
Li Wen,
Kashiwamura Shinichiro,
Ueda Haruyasu,
Sekiyama Atsuo,
Okamura Haruki
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0706431
Subject(s) - biology , cd8 , cytotoxic t cell , interleukin 21 , microbiology and biotechnology , population , il 2 receptor , t cell , immunology , immune system , in vitro , biochemistry , medicine , environmental health
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 ∼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‐18Rβ 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.