Hormonal regulation of CD4+ T-cell responses in coxsackievirus B3-induced myocarditis in mice
Hormonal regulation of CD4+ T-cell responses in coxsackievirus B3-induced myocarditis in mice
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DOI：
10.1128/jvi.73.6.4689-4695.1999
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发表时间：
1999-06-01
影响因子：
5.4
通讯作者：
Newell, MK
中科院分区：
文献类型：
--
作者：
Huber, SA;Kupperman, J;Newell, MK
柯萨奇病毒B3感染会导致雄性B1Tg.E阿尔法小鼠的显著心脏炎症，但雌性B1Tg.E阿尔法小鼠则不会。这种疾病易感性的性别差异与在使用睾酮的动物中选择性地诱导CD4(+)Th1(伽马干扰素阳性)细胞反应有关，而雌二醇促进优先的CD4(+)Th2(白细胞介素IL阳性[IL-4(+)])细胞反应。CD4(+)T细胞免疫偏离的差异不能用B7-1或B7-2表达的变化来解释。感染显著上调了这两种分子，但雌二醇组和睾丸酮组之间没有发现差异。在雄性和接受睾酮治疗的雄性和雌性小鼠中，发现表达伽马增量T细胞受体的激活(CD69(+))T细胞的数量显著增加。在体内，使用单抗去除γ-增量(+)细胞可抑制心肌炎，并导致Th1反应表型向Th2反应表型的转变。综上所述，我们的结果表明，睾酮通过促进伽马增量(+)细胞的激活来促进CD4(+)Th1细胞的反应和心肌炎。
Coxsackievirus B3 infection causes significant cardiac inflammation in male, but not female, B1.Tg.E alpha mice. This gender difference in disease susceptibility correlates with selective induction of CD4(+) Th1 (gamma interferon-positive) cell responses in animals with testosterone, whereas estradiol promotes preferential CD4(+) Th2 (interleukin-il positive [IL-4(+)]) cell responses. Differences in immune deviation of CD4(+) T cells cannot be explained by variation in B7-1 or B7-2 expression. Infection significantly upregulated both molecules, but no differences were detected between estradiol- and testosterone-treated groups. Significantly increased numbers of activated (CD69(+)) T cells expressing the gamma delta T-cell receptor were found in male and testosterone-treated male and female mice. In vivo depletion of gamma delta(+) cells by using monoclonal antibodies inhibited myocarditis and resulted in a shift from a Th1 to Th2 response phenotype. Taken together, our results indicate that testosterone promotes a CD4(+) Th1 cell response and myocarditis by promoting increased gamma delta(+) cell activation.