Increased natural CD4+CD25+ regulatory T cells and their suppressor activity do not contribute to mortality in murine polymicrobial sepsis
Increased natural CD4+CD25+ regulatory T cells and their suppressor activity do not contribute to mortality in murine polymicrobial sepsis
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DOI：
10.4049/jimmunol.177.11.7943
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发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Moldawer, Lyle L.
中科院分区：
文献类型：
--
作者：
Scumpia, Philip O.;Delano, Matthew J.;Moldawer, Lyle L.
调节性T细胞（Treg），包括天然的CD 4（+）CD 25（+）Treg和产生IL-10的诱导型T调节性1型（T（R）1）细胞，维持耐受性并抑制自身免疫。最近，在脓毒症患者的血液中观察到增加的TbR百分比，并且体外活化的TbR显示出预防多微生物脓毒症死亡率。内源性凝血酶是否有助于脓毒症的结局仍不清楚。与假手术组小鼠相比，盲肠结扎和穿孔诱导的多微生物脓毒症导致脾THP数量增加。脓毒症小鼠脾脏CD 4（+）CD 25（+）T细胞表达更高水平的Foxp 3 mRNA，并且是CD 4（+）CD 25（-）T效应细胞增殖的更有效抑制剂。从脓毒症小鼠分离的CD 4（+）T细胞在刺激后显示细胞内IL-10染色增加，表明T，I细胞也可能在脓毒症中升高。令人惊讶的是，总CD 4（+）或CD 4（+）CD 25（+）群体的抗体耗竭并不影响死亡率。此外，在CD 25或IL-10缺失小鼠和野生型同窝小鼠之间没有发现存活结果的差异，表明Treg或T（R）1产生的IL-10不是存活所必需的。这些结果表明，尽管脓毒症导致Treg数量的相对增加并增加其抑制功能，但它们的存在对该模型中的总存活率没有显著贡献。
Regulatory T cells (Tregs), including natural CD4(+)CD25(+) Tregs and inducible IL-10 producing T regulatory type 1 (T(R)1) Cells' maintain tolerance and inhibit autoimmunity. Recently, increased percentages of Tregs have been observed in the blood of septic patients, and ex vivo-activated Tregs were shown to prevent polymicrobial sepsis mortality. Whether endogenous Tregs contribute to sepsis outcome remains unclear. Polymicrobial sepsis, induced by cecal ligation and puncture, caused an increased number of splenic Tregs compared with sham-treated mice. Splenic CD4(+)CD25(+) T cells from septic mice expressed higher levels of Foxp3 mRNA and were more efficient suppressors of CD4(+)CD25(-) T effector cell proliferation. Isolated CD4(+) T cells from septic mice displayed increased intracellular IL-10 staining following stimulation, indicating that T,I cells may also be elevated in sepsis. Surprisingly, Ab depletion of total CD4(+) or CD4(+)CD25(+) populations did not affect mortality. Furthermore, no difference in survival outcome was found between CD25 or IL-10 null mice and wild-type littermates, indicating that Treg or T(R)1-generated IL-10 are not required for survival. These results demonstrate that, although sepsis causes a relative increase in Treg number and increases their suppressive function, their presence does not contribute significantly to overall survival in this model.