Mechanism by which pertussis toxin breaks unresponsiveness of delayed-type hypersensitivity to sheep red blood cells in mice

Abstract The mechanism by which pertussis toxin (PT) breaks the unresponsiveness of delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) was examined in B10 mice. The unresponsiveness of DTH was induced in mice by iv injection of 10 9 SRBC and broken antigen-specifically by iv injection of 500 ng of PT into mice 1 or more days after SRBC injection. The restored DTH response in the SRBC-primed and PT-treated mice was accompanied by the appearance of Lyt-1-positive splenic T cells, capable of mediating DTK, fractionated in the low-density layers on a discontinuous bovine serum albumin density gradient. To examine the action of PT on the appearance of the DTH-effector cells, the splenic T cells from 10 9 SRBC-primed mice were treated with 100 ng/ml of PT for 60 min in vitro and then transferred into naive recipient mice. The PT-treated T cells acquired the ability to manifest DTH in the recipient mice several days after transfer. A large proportion of them were Lyt-1-positive small cells fractionated in the high-density layers before transfer and transformed into DTH-effector cells fractionated in the low-density layers in the recipient mice after transfer. Moreover, the ability of the PT-treated cells to manifest DTH on transfer was resistant to treatment with mitomycin C. These results suggest that PT acts on the sensitized, small Lyt-1-positive T cells from the unresponsive mice to differentiate them into large T-cell blasts, capable of mediating DTH, as one of the mechanisms by which PT breaks the unresponsiveness of DTH to SRBC.