Vγ1+ T cells suppress and Vγ4+ T cells promote susceptibility to coxsackievirus B3-induced myocarditis in mice
Vγ1+ T cells suppress and Vγ4+ T cells promote susceptibility to coxsackievirus B3-induced myocarditis in mice
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DOI：
10.4049/jimmunol.165.8.4174
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发表时间：
2000-10-15
影响因子：
4.4
通讯作者：
O'Brien, RL
中科院分区：
文献类型：
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作者：
Huber, SA;Graveline, D;O'Brien, RL
C57BL/6 小鼠的柯萨奇病毒 B3 感染表达 MHC II 类 IA 但不表达 IE Ag，导致病毒在心脏中复制，但心肌炎程度极低。相比之下，B1.Tg.E α 小鼠，即转基因诱导表达 IE Ag 的 C57BL/6 小鼠，在柯萨奇病毒 B3 感染后出现明显的心肌炎。尽管炎症损伤存在差异，但 C57BL16 和 B1.Tg.E α 小鼠之间的心脏病毒滴度相似。通过基因操作（γ δ 敲除（ko））从任一菌株中去除γ δ T细胞会改变疾病表型，C57BL/6γ δ KO小鼠显示出心肌炎增加，相反，B1.Tg.E αγ δ KO小鼠显示出心脏炎症减少。流式细胞术显示两种品系的 γ δ 细胞亚群存在差异，其中 V γ 1 在 C57BL16 小鼠中占主导地位，而 V γ 4 在 B1.Tg.E α 小鼠中占主导地位。这表明这两个 V gamma 定义的子集可能具有不同的功能。为了测试这种可能性，我们使用 mAb 注射来耗尽每个子集。耗尽 V gamma 1 细胞的小鼠表现出增强的心肌炎，而耗尽 V gamma 4 细胞的小鼠抑制了心肌炎，将富集的 V gamma 4(+) 细胞过继输注至 C57BL/6 和 B1.Tg.E alpha gamma delta ko 菌株证实 V gamma 4 子集促进了心肌炎，Th 子集分析表明 V gamma 1(+)细胞使CD4(+)T细胞偏向Th2细胞反应为主，而Vγ4(+)细胞使CD4(+)T细胞偏向Th1细胞反应为主。
Coxsackievirus B3 infections of C57BL/6 mice, which express the MHC class II IA but not IE Ag, results in virus replication in the heart but minimal myocarditis. In contrast, B1.Tg.E alpha mice, which are C57BL/6 mice transgenically induced to express IE Ag, develop significant myocarditis upon Coxsackievirus B3 infection. Despite this difference in inflammatory damage, cardiac virus titers are similar between C57BL16 and B1.Tg.E alpha mice. Removing gamma delta T cells from either strain by genetic manipulation (gamma delta knockout(ko)) changes the disease phenotype, C57BL/6 gamma delta ko mice show increased myocarditis, In contrast, B1.Tg.E alpha gamma delta ko mice show decreased cardiac inflammation. Flow cytometry revealed a difference in the gamma delta cell subsets in the two strains, with V gamma 1 dominating in C57BL16 mice, and V gamma 4 predominating B1.Tg.E alpha mice. This suggests that these two V gamma-defined subsets might have different functions. To test this possibility, we used mAb injection to deplete each subset. Mice depleted of V gamma 1 cells showed enhanced myocarditis, whereas those depleted of V gamma 4 cells suppressed myocarditis, Adoptively transfusing enriched V gamma 4(+) cells to the C57BL/6 and B1.Tg.E alpha gamma delta ko strains confirmed that the V gamma 4 subset promoted myocarditis, Th subset analysis suggests that V gamma 1(+) cells biased the CD4(+) T cells to a dominant Th2 cell response, whereas V gamma 4(+) cells biased CD4(+) T cells toward a dominant Th1 cell response.