Hultman C S, Cairns B A, Yamamoto H, deSerres S, Frelinger J A, Meyer A A
Department of Surgery, University of North Carolina, Chapel Hill 27599-7210, USA.
J Burn Care Rehabil. 1995 Nov-Dec;16(6):573-80.
Burn injury impairs cellular immunity, increases the risk of viral infection, and delays allograft rejection, but little is known about its effect on antigen processing and cytotoxic T-lymphocyte (CTL) function. This study examined the effect of burn injury on alloantigen sensitization with an in vivo model of second-set rejection and in vitro assays of CTL alloreactivity. Anesthetized CBA mice (n = 95) received a 0%, 20%, or 40% full-thickness contact burn that was partially excised 3 days later and covered with autograft or C57BL/6 allograft. Two weeks after the burn was inflicted, mice were challenged with second-set tail allografts, which were observed for rejection. Median graft survival times were compared by Wilcoxon rank and chi-squared analysis. Additional CBA mice (n = 24) underwent similar burn injury, excision, and grafting. Splenocytes were harvested 2 weeks later and were used as CTL effectors against radiolabeled targets. Dilution curves of target lysis were compared by analysis of variance. Forty percent burn injury prolonged unprimed allograft survival from 13 to 15 days (p < 0.01) but had a greater effect on primed allograft survival, which increased from 9 to 12.5 days (p < 0.01). Furthermore, a 40% burn eliminated the influence of priming, resulting in second-set graft survival similar to that of mice in an unburned, unprimed control group (12.5 vs. 13 days, NS). Whereas 20% burn injury did not inhibit CTL priming, a 40% burn profoundly impaired CTL function (p < 0.001), which recovered only after 6 days of in vitro allostimulation. Burn injury inhibits both alloantigen priming and the immunologic memory of CTLs as a function of burn size. This impairment in alloantigen processing helps to explain defects in cellular immunity and suggests a mechanism for prolonged allograft survival and decreased viral resistance after burn injury occurs.
烧伤会损害细胞免疫，增加病毒感染风险，并延迟同种异体移植排斥反应，但关于其对抗原处理和细胞毒性T淋巴细胞（CTL）功能的影响却知之甚少。本研究通过二次排斥反应的体内模型和CTL同种异体反应性的体外试验，研究了烧伤对同种异体抗原致敏的影响。将麻醉的CBA小鼠（n = 95）给予0%、20%或40%的全层接触烧伤，3天后部分切除烧伤部位，并用自体移植或C57BL/6同种异体移植覆盖。烧伤后两周，用二次尾部同种异体移植对小鼠进行攻击，并观察排斥反应。通过Wilcoxon秩和检验及卡方分析比较移植的中位存活时间。另外24只CBA小鼠接受类似的烧伤、切除和移植。两周后收集脾细胞，并用作针对放射性标记靶标的CTL效应细胞。通过方差分析比较靶细胞裂解的稀释曲线。40%的烧伤使未致敏的同种异体移植存活时间从13天延长至15天（p < 0.01），但对致敏的同种异体移植存活时间影响更大，从9天增加到12.5天（p < 0.01）。此外，40%的烧伤消除了致敏的影响，导致二次移植存活时间与未烧伤、未致敏对照组小鼠相似（12.5天对13天，无显著性差异）。虽然20%的烧伤不抑制CTL致敏，但40%的烧伤严重损害CTL功能（p < 0.001），仅在体外同种异体刺激6天后才恢复。烧伤会抑制同种异体抗原致敏以及CTL的免疫记忆，且这种抑制作用与烧伤面积有关。这种同种异体抗原处理的损害有助于解释细胞免疫缺陷，并提示了烧伤后同种异体移植存活时间延长和病毒抵抗力降低的机制。
