Prevention of superantigen-induced down-regulation of T-cell mediated cytotoxic activity by IL-2 in vivo.
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 severely reduced cytotoxic activity in the spleen, which correlated with a reduced number of sea-responsive T-cell receptor (TCR)-V beta 11+ CD8+ cells. Studies of purified TCR-V beta 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 alpha + cells, suggesting that administration of IL-2 maintained IL-2 responsiveness among CD8+ cells. Studies of sorted TCR-V beta 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.
Belfrage
H
H
Department of Cell and Molecular Biology, Lund University, Sweden.
Dohlsten
M
M
Hedlund
G
G
Kalland
T
T
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D007108:Immune Tolerance; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018089:Superantigens / Q000276:immunology*
D004768:Enterotoxins; D007376:Interleukin-2; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal