DIFFERENTIAL REGULATION OF IL-9-EXPRESSION AFTER INFECTION WITH LEISHMANIA-MAJOR IN SUSCEPTIBLE AND RESISTANT MICE
DIFFERENTIAL REGULATION OF IL-9-EXPRESSION AFTER INFECTION WITH LEISHMANIA-MAJOR IN SUSCEPTIBLE AND RESISTANT MICE
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DOI：
10.1016/s0171-2985(11)80414-6
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发表时间：
1993-12-01
期刊：
影响因子：
2.8
通讯作者：
ROLLINGHOFF, M
中科院分区：
文献类型：
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作者：
GESSNER, A;BLUM, H;ROLLINGHOFF, M
IL-9是一种多效性淋巴因子，其活性之一是刺激某些CD 4（+）T淋巴细胞的生长。在小鼠皮肤利什曼病中，根据宿主小鼠品系的遗传背景，在感染硕大利什曼原虫后，在抗性C57 BL/6小鼠中主要是Th 1或在易感BALB/c小鼠中主要是Th 2型CD 4（+）T细胞发生剧烈增殖。major）。由于对IL-9的参与知之甚少，因此通过比较其在抗性和敏感小鼠的血清中的存在及其在脾和淋巴结中的表达动力学来评估这种细胞因子在其免疫调节功能方面的可能作用。对主要感染的小鼠进行IL-9的功能测试。此外，还采用PCR辅助检测小鼠器官中IL-9 mRNA的表达，以及再刺激淋巴结和脾细胞培养上清液中淋巴因子的测定。我们发现，尽管在BALB/c和C57 BL/6小鼠的血清中均未检测到具有功能活性的IL-9，但IL-9在体外抗原再刺激后产生，并且在针对L.少校感染后不久，可以观察到IL-9表达的动力学没有主要差异，其最大值在感染后第5和第7天之间。然而，在敏感的BALB/c小鼠中的产生率较高。在无胸腺BALB/c nu/nu小鼠和去除CD 4（+）T细胞的小鼠中，在mRNA水平上没有检测到IL-9的产生，并且在用L.体外主要抗原。用环孢菌素A治疗感染的小鼠在体外测试时消除了抗原特异性IL-9的产生，而不影响其在多克隆T细胞刺激后的产生。阳性选择的纯化的CD 4（+）T细胞完全能够产生IL-9。从感染后4周开始，仅在BALB/c小鼠中观察到IL-9合成，这与这些小鼠中抗原特异性Th 2型辅助性T细胞的扩增相关。用中和性抗IL-4 mAb治疗BALB/c小鼠（一种已知导致感染BALB/c小鼠随后治愈的方案）可抑制晚期IL-9合成。
IL-9 is a pleiotropic lymphokine, one of its activities being the growth stimulation of certain CD4(+) T lymphocytes. In murine cutaneous leishmaniasis, depending on the genetic background of the host mouse strain, vigorous proliferation of either mainly Th1 in resistant C57BL/6 mice or Th2-type CD4(+) T cells in susceptible BALB/c mice occurs after infection with Leishmania major (L. major). Since little is known about the involvement of IL-9, the possible role of this cytokine with regard to its immunregulatory function was evaluated by comparing its presence in the serum and its expression kinetics in spleen and lymph nodes in resistant and susceptible mice.To this sera of L. major-infected mice were tested functionally for IL-9. In addition the PCR-aided detection of IL-9 mRNA in organs of mice and measurement of the lymphokine in supernatants of restimulated lymph node and spleen cell cultures were used. We show here that although no functionally active IL-9 was detected in sera of both BALB/c and C57BL/6 mice, IL-9 is produced after in vitro antigenic restimulation and its mRNA was found to be expressed in lymph nodes and spleens during an immune response against L. major. Shortly after infection no principal differences in the kinetics of IL-9 expression could be observed, which had its maximum between day 5 and 7 after infection. The rate of production however was higher in the susceptible BALB/c mice. In athymic BALB/c nu/nu mice and in mice depleted of CD4(+) T cells no IL-9 production was detectable in vivo at the level of mRNA and no IL 9 was produced after stimulation with L. major antigen in vitro. Treatment df infected mice with cyclosporin A ablates antigen-specific IL-9 production when tested in vitro without affecting its production after polyclonal T cell stimulation. Positively selected, purified CD4(+) T cells were fully capable of producing IL-9. From 4 weeks after infection, IL-9 synthesis was observed only in BALB/c mice, correlating with the expansion of antigen-specific Th2 type T helper cells in these mice. Treatment of BALB/c mice with neutralizing anti-IL-4 mAb, a regimen known to lead to subsequent cure of infected BALB/c mice, suppressed late IL-9 synthesis.