Effector CD8+ T lymphocytes against liver stages of Plasmodium yoelii do not require gamma interferon for antiparasite activity

Effector CD8+ T lymphocytes against liver stages of Plasmodium yoelii do not require gamma interferon for antiparasite activity
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DOI:
10.1128/iai.00471-08
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发表时间:
2008-08-01
影响因子:
3.1
通讯作者:
Zavala, Fidel
Zavala, Fidel
中科院分区:
医学2区
文献类型:
--
作者:
Chakravarty, Sumana;Baldeviano, G. Christian;Zavala, Fidel

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针对疟疾寄生虫肝脏阶段的保护性免疫应答关键地需要CD 8(+)T细胞。虽然这些细胞抑制寄生虫发育的效应机制的性质尚不清楚,但基于间接证据,γ干扰素(IFN-γ)的关键作用已被广泛假定。然而,在对该病原体的保护性免疫中对CD 8(+)T细胞介导的IFN-γ产生的需求尚未直接测试。在这份报告中,我们使用过继转移策略与环子孢子(CS)蛋白特异性转基因T细胞,以检查CD 8(+)T细胞衍生的IFN-γ的生产在约氏疟原虫感染小鼠的作用。我们发现,尽管幼稚IFN-γ缺陷CS特异性转基因T细胞的扩增略有减少,但其抗寄生虫活性保持不变。此外,过继转移的IFN-γ缺陷型CD 8(+)T细胞在限制幼稚小鼠中寄生虫生长方面与其野生型对应物一样有效。综上所述,这些研究表明,CS特异性CD 8(+)T细胞分泌IFN-γ对保护小鼠免受活子孢子攻击并不重要。
The protective immune response against liver stages of the malaria parasite critically requires CD8(+) T cells. Although the nature of the effector mechanism utilized by these cells to repress parasite development remains unclear, a critical role for gamma interferon (IFN-gamma) has been widely assumed based on circumstantial evidence. However, the requirement for CD8(+) T-cell-mediated IFN-gamma production in protective immunity to this pathogen has not been directly tested. In this report, we use an adoptive transfer strategy with circumsporozoite (CS) protein-specific transgenic T cells to examine the role of CD8(+) T-cell-derived IFN-gamma production in Plasmodium yoelii-infected mice. We show that despite a marginal reduction in the expansion of naive IFN-gamma-deficient CS-specific transgenic T cells, their antiparasite activity remains intact. Further, adoptively transferred IFN-gamma-deficient CD8(+) T cells were as efficient as their wild-type counterparts in limiting parasite growth in naive mice. Taken together, these studies demonstrate that IFN-gamma secretion by CS-specific CD8(+) T cells is not essential to protect mice against live sporozoite challenge.