A burn induced Ly-2 suppressor T cell lowers resistance to bacterial infection

Abstract

Suppressor T cell activity after major burn injury in a murine model has been well characterized. Suppressor cells have also been demonstrated in patients after major burn, and suppressor cell activity has been temporally correlated with septic episodes. A splenic Ly-2 T suppressor effector (Tse) cell appearing 7 days after a 30% full thickness burn has been identified in a murine model. A rat monoclonal antibody (14-8c3-12) directed against a factor produced by the Tse cell (Tsef) can enhance depressed in vitro mixed lymphocyte reaction (MLR) responses of Day 7 burn spleen cells without enhancing control spleen cell activity. Additionally, 14-8c3-12 can block the suppressive effect of these burn T cells on normal T cells. A cecal ligation and puncture (CLP) model using a 25-gauge needle (LD 15) was used to assess the contribution of burn T cells to post-CLP mortality. Normal spleen cells injected into syngeneic recipients followed by CLP did not affect mortality (13%). Burn spleen cells injected into normal recipients enhanced mortality sixfold (90%) after CLP. The effect could be reversed by removing Ly-2 T cells (30% mortality) but not Ly-I T cells (100% mortality) prior to cell transfer. Simultaneous injection of 14-8c3-12 antibody with burn T cells reduced mortality after CLP significantly (20%). Injection of 14-8c3-12 did not improve survival after CLP in control animals not injected with burn T cells (20%). Ly-2 T suppressor effector cells found in the spleens of mice 7 days postburn enhance the lethality of a purely bacterial septic challenge. A monoclonal antibody to the Tsef can reverse this effect in vivo.