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Prevention of superantigen‐induced down‐regulation of T‐cell mediated cytotoxic activity by IL‐2 in vivo
Author(s) -
BELFRAGE H.,
DOHLSTEN M.,
HEDLUND G.,
KALLAND T.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00030.x
Subject(s) - cytotoxic t cell , cd8 , biology , ctl* , t cell , immunology , chemistry , microbiology and biotechnology , immune system , in vitro , biochemistry
Administration of staphylococcal enterotoxin A (SEA) to mice induces profound activation, cytokine production and cytotoxic activity of both CD4 + and CD8 + T cells, but subsequently activated cells are deleted or become anergic. This study demonstrates that administration of interleukin‐2 (IL‐2) can prevent sea‐induced hyporesponsiveness in CD8 + cytotoxic T lymphocytes (CTL). Repeated injections with sea every fourth day resulted in severly reduced cytotoxic activity in the spleen, which correlated with a reduced number of sea‐responsive T‐cell receptor (TCR)‐V β 11 + CD8 + cells. Studies of purified TCR‐V β 11 + CD8 + cells showed that they possessed intact cytotoxic activity per cell compared with cells from mice given a single injection of SEA, indicating that deletion was the main mechanism for the reduced cytotoxic activity. Combined treatment with SEA and IL‐2 increased the number of cytotoxic cells in the spleen after each SEA injection and prevented the down‐regulation of cytotoxic activity. Increased cytotoxic activity could be related to increased number and proliferation of CD8 + IL‐2R α + cells, suggesting that administration of IL‐2 maintained IL‐2 responsiveness among CD8 + cells. Studies of sorted TCR‐V β 11 + CD8 + cells demonstrated that combined treatment with SEA and IL‐2 also increased cytotoxic activity per cell compared with treatment with SEA alone. Taken together, IL‐2 administration in vivo augmented SEA‐induced expansion of T cells as well as the cytotoxic activity per CTL, and prevented SEA‐induced cell deletion.