C3 promotes expansion of CD8+ and CD4+ T cells in a Listeria monocytogenes infection.
C3 promotes expansion of CD8+ and CD4+ T cells in a Listeria monocytogenes infection.
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DOI：
10.4049/jimmunol.0801191
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发表时间：
2009-09-01
期刊：
影响因子：
--
通讯作者：
Suresh M
中科院分区：
文献类型：
--
作者：
Nakayama Y;Kim SI;Kim EH;Lambris JD;Sandor M;Suresh M
已知C3是急性病毒感染期间T细胞最佳扩增所需的。然而，尚未确定T细胞对细胞内细菌感染的应答是否需要C3。因此，我们已经研究了C3引起对单核细胞增生李斯特菌（LM）的有效T细胞应答的要求。我们发现，在对LM的初级应答期间，抗原特异性CD8和CD4 T细胞的扩增在C3活性的情况下显著减少。进一步的研究表明，与流感病毒感染不同，C3对LM特异性T细胞应答的调节可能不涉及下游效应子C5a。此外，减少对LM的T细胞应答与C3缺陷小鼠外周T细胞区室中的DC成熟缺陷或发育异常无关。涉及将C3缺陷型CD8 T细胞过继转移到野生型小鼠的C3充足环境中的实验表明，这些T细胞不具有内在的增殖缺陷，并且C3的旁分泌来源将足以用于体内CD8 T细胞的克隆扩增。然而，用塑料固定的抗CD3刺激纯化的C3缺陷型CD8 T细胞表明，C3直接促进T细胞增殖，而不依赖于其对抗原呈递细胞的影响。基于这些发现，我们提出，减少T细胞对LM在C3缺陷小鼠可能至少部分是由于缺乏直接影响的C3对T细胞。这些研究进一步加深了我们对C3介导的T细胞免疫对胞内病原体的调节的理解。
It is known that C3 is required for optimal expansion of T cells during acute viral infections. However, it is not yet determined whether T cell responses to intracellular bacterial infections require C3. Therefore, we have investigated the requirement for C3 to elicit potent T cell responses to Listeria monocytogenes (LM). We show that expansion of antigen-specific CD8 and CD4 T cells during a primary response to LM was markedly reduced in the absence of C3 activity. Further studies indicated that, unlike in an influenza virus infection, the regulation of LM-specific T cell responses by C3 might not involve the downstream effector C5a. Moreover, reduced T cell responses to LM was not linked to defective maturation of DCs or developmental anomalies in the peripheral T cell compartment of C3-deficient mice. Experiments involving adoptive transfer of C3-deficient CD8 T cells into the C3-sufficient environment of wild type mice showed that these T cells do not have intrinsic proliferative defects and paracrine source of C3 will suffice for clonal expansion of CD8 T cells in vivo. However, stimulation of purified C3-deficient CD8 T cells by plastic-immobilized anti-CD3 showed that C3 promotes T cell proliferation directly, independent of its effects on antigen-presenting cells. Based on these findings, we propose that diminished T cell responses to LM in C3-deficient mice might be at least in part due to lack of direct effects of C3 on T cells. These studies have furthered our understanding of C3-mediated regulation of T cell immunity to intracellular pathogens.
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影响因子：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
32.4
作者：
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通讯作者：
BEVAN, MJ
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4.4
作者：
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通讯作者：
Erdei, A
影响因子：
82.9
作者：
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通讯作者：
Bachmann, MF
影响因子：
56.9
作者：
HUANG, S;HENDRIKS, W;AGUET, M
通讯作者：
AGUET, M