PREVENTION OF SUPERANTIGEN-INDUCED DOWN-REGULATION OF T-CELL MEDIATEDCYTOTOXIC ACTIVITY BY IL-2 IN-VIVO

Administration of staphylococcal enterotoxin A (SEA) to mice induces p rofound activation, cytokine production and cytotoxic activity of both CD4(+) and CD8(+) T cells, but subsequently activated cells are delet ed or become anergic. This study demonstrates that administration of i nterleukin-2 (IL-2) can prevent sea-induced hyporesponsiveness in CD8( +) cytotoxic T lymphocytes (CTL). Repeated injections with sea every f ourth day resulted in severly reduced cytotoxic activity in the spleen , which correlated with a reduced number of sea-responsive T-cell rece ptor (TCR)-V beta 11(+)CD8(+) cells. Studies of purified TCR-V beta 11 (+)CD8(+) cells showed that they possessed intact cytotoxic activity p er cell compared with cells from mice given a single injection of SEA, indicating that deletion was the main mechanism for the reduced cytot oxic activity. Combined treatment with SEA and IL-2 increased the numb er of cytotoxic cells in the spleen after each SEA injection and preve nted the down-regulation of cytotoxic activity. Increased cytotoxic ac tivity could be related to increased number and proliferation of CD8()IL-2R alpha(+) cells, suggesting that administration of IL-2 maintain ed IL-2 responsiveness among CD8(+) cells. Studies of sorted TCR-V bet a 11(+)CD8(+) cells demonstrated that combined treatment with SEA and IL-2 also increased cytotoxic activity per cell compared with treatmen t with SEA alone. Taken together, IL-2 administration in vivo augmente d SEA-induced expansion of T cells as well as the cytotoxic activity p er CTL, and prevented SEA-induced cell deletion.