Signaling through the T1/ST2 molecule is not necessary for Th2 differentiation but is important for the regulation of type 1 responses in nonhealing Leishmania major infection
Signaling through the T1/ST2 molecule is not necessary for Th2 differentiation but is important for the regulation of type 1 responses in nonhealing Leishmania major infection
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DOI：
10.1128/iai.71.4.1961-1971.2003
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发表时间：
2003-04-01
影响因子：
3.1
通讯作者：
Müller, I
中科院分区：
文献类型：
--
作者：
Kropf, P;Herath, S;Müller, I
T1/ST 2是选择性表达于2型T辅助（Th 2）效应细胞上的稳定的细胞表面标志物。由于在易感的BALB/c小鼠中，主要利什曼原虫感染的不愈合归因于极化的Th 2应答，我们使用抗T1/ST 2单克隆抗体（MAb）或T1-Fc融合蛋白来研究CD 4（+）T1/ST 2（+）Th 2细胞在实验性利什曼原虫病中的作用。我们发现，干扰T1/ST 2信号对病变发展或寄生虫复制没有影响;然而，它诱导了显著更高的1型反应和增强的CD 4（+）T细胞对白细胞介素12（IL-12）的反应能力。令人惊讶的是，即使在Th 1应答升高的情况下，在用抗T1/ST 2 MAb或T1-Fc融合蛋白处理的小鼠组中，抗原特异性2型细胞因子的产生也没有改变。为了进一步表征这种Th 2应答，我们评估了CD 4（+）T细胞的细胞因子谱，发现干扰T1/ST 2信号传导不会改变CD 4（+）T1/ST 2（+）T细胞的细胞因子谱。这些结果表明，T1/ST 2信号传导对于幼稚CD 4（+）T细胞分化为抗原特异性CD 4（+）T1/ST 2（+）Th 2细胞不是必需的。除了CD 4（+）T1/ST 2（+）T细胞外，我们还检测到另一个CD 4（+）Th 2细胞亚群，其T1/ST 2表达阴性，可在体内响应L.严重感染综上所述，我们的结果表明，CD 4 + T1/ST 2 + Th 2细胞，而不是CD 4（+）T1/ST 2（-）Th 2细胞可以下调Th 1反应在不愈合的L。通过不依赖于IL-4或IL-10的机制的主要感染。
T1/ST2 is a stable cell surface marker selectively expressed on type 2 T helper (Th2) effector cells. Since nonhealing Leishmania major infections in susceptible BALB/c mice have been ascribed to a polarized Th2 response, we used an anti-T1/ST2 monoclonal antibody (MAb) or a T1-Fc fusion protein to investigate the role of CD4(+) T1/ST2(+) Th2 cells in experimental leishmaniasis. We show that interfering with T1/ST2 signaling had no effect on lesion development or parasite replication; however, it induced a significantly higher type 1 response and an enhanced capacity of CD4(+) T cells to respond to interleukin 12 (IL-12). Surprisingly, even in the presence of an elevated Th1 response, the production of antigen-specific type 2 cytokines was not altered in the group of mice treated with the anti-T1/ST2 MAb or the T1-Fc fusion protein. To characterize further this Th2 response, we assessed the cytokine profile of CD4(+) T cells and found that interfering with T1/ST2 signaling did not alter the cytokine profile of CD4(+) T1/ST2(+) T cells. These results show that T1/ST2 signaling is not necessary for the differentiation of naive CD4(+) T cells into antigen-specific CD4(+) T1/ST2(+) Th2 cells. In addition to CD4(+) T1/ST2(+) T cells, we detected another subpopulation of CD4(+) Th2 cells, negative for the expression of T1/ST2, that could differentiate in vivo in response to L. major infection. Taken together, our results suggest that CD4+ T1/ST2+ Th2 cells but not CD4(+) T1/ST2(-) Th2 cells can downregulate the Th1 response during the course of a nonhealing L. major infection through a mechanism that is independent of IL-4 or IL-10.