Thermal injury-plus-sepsis contributes to a substantial deletion of intestinal mesenteric lymph node CD4 T cell via apoptosis.
Thermal injury-plus-sepsis contributes to a substantial deletion of intestinal mesenteric lymph node CD4 T cell via apoptosis.
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DOI：
10.7150/ijbs.3.393
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发表时间：
2007-09-12
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
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伴有脓毒症并发症的热损伤（TI）仍然是一个严重的临床问题。这类患者主要关注的问题之一是与肠道CD4 + T淋巴细胞功能紊乱相关的免疫抑制。先前对热损伤/脓毒症患者以及热损伤/脓毒症动物模型的大量研究表明，肠道CD4 + T细胞对抗原/有丝分裂原的反应性降低。这种低反应性可能会显著增加受伤宿主对病原体的易感性，包括那些从宿主肠腔转移的病原体。我们之前的研究表明，虽然单独的热损伤或脓毒症会导致肠道CD4 + T细胞的增殖和白细胞介素 - 2（IL - 2）产生受到抑制，但本研究显示肠系膜淋巴结（MLN）CD4 + T细胞通过凋亡大量缺失。因此，热损伤合并脓毒症不仅导致CD4 + T细胞增殖/IL - 2产生受抑制，还对CD4 + T细胞的存活能力产生重大影响。这些发现使我们得出结论：虽然单独的热损伤可导致细胞介导的反应减弱，但CD4 + T细胞存活没有明显变化；而伴有脓毒症并发症的热损伤会导致CD4 + T细胞死亡以及细胞介导反应的不可逆丧失。后者可能是热损伤合并严重感染的受伤宿主高发病率和高死亡率的原因。
Thermal injury (TI) with septic complications continues to be a serious clinical problem. One of the main concerns in such patients is immunosuppression related to functional derangements in intestinal CD4+ T lymphocytes. Extensive previous studies in thermal injury/septic patients and animal models of thermal injury/sepsis have shown decreased responsiveness of intestinal CD4+ T cells to antigen/mitogen. This hyporesponsiveness could significantly contribute to increase injured host susceptibility to pathogens including those translocating from host's gut lumen. Our previous studies indicated that while thermal injury or sepsis alone lead to suppressed proliferation and IL-2 production of intestinal CD4+ T cells, this study showed a substantial deletion via apoptosis of the Mesenteric Lymph Nodes (MLN) CD4+ T cells. Hence, thermal injury-plus-sepsis contributes not only to suppressed CD4+ T proliferation/IL-2 production but also to a substantial modulation of CD4+ T cell survivability. These findings allow us to conclude that while thermal injury alone can produce attenuated cell mediated responses without an overt change in CD4+ T cell survival, thermal injury with septic complications causes CD4+ T cell death and an irreversible loss of cell-mediated responses. The latter happening could be responsible for high morbidity and mortality in the injured host afflicted with thermal injury plus a critical infection.