Kupper T S, Baker C C, Ferguson T A, Green D R
J Surg Res. 1985 Jun;38(6):606-12. doi: 10.1016/0022-4804(85)90082-4.
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 (LD15) 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-1 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.
在小鼠模型中,严重烧伤后抑制性T细胞的活性已得到充分表征。在严重烧伤患者中也已证实存在抑制性细胞,并且抑制性细胞活性与脓毒症发作在时间上相关。在小鼠模型中,已鉴定出在30%全层烧伤7天后出现的脾脏Ly-2 T抑制效应细胞(Tse)。一种针对Tse细胞产生的因子(Tsef)的大鼠单克隆抗体(14-8c3-12)可以增强第7天烧伤脾细胞体外混合淋巴细胞反应(MLR)的抑制反应,而不增强对照脾细胞的活性。此外,14-8c3-12可以阻断这些烧伤T细胞对正常T细胞的抑制作用。使用25号针头的盲肠结扎穿刺(CLP)模型(LD15)来评估烧伤T细胞对CLP后死亡率的影响。将正常脾细胞注入同基因受体后进行CLP,对死亡率没有影响(13%)。将烧伤脾细胞注入正常受体后,CLP后的死亡率提高了六倍(90%)。在细胞转移前去除Ly-2 T细胞(死亡率30%)可逆转这种效应,但去除Ly-1 T细胞(死亡率100%)则不能。将14-8c3-12抗体与烧伤T细胞同时注射可显著降低CLP后的死亡率(20%)。在未注射烧伤T细胞的对照动物中,注射14-8c3-12并不能改善CLP后的生存率(20%)。烧伤后7天在小鼠脾脏中发现的Ly-2 T抑制效应细胞可增强单纯细菌性脓毒症攻击的致死性。针对Tsef的单克隆抗体可在体内逆转这种效应。