CD40L-deficient mice show deficits in antiviral immunity and have an impaired memory CD8+ CTL response.
CD40L-deficient mice show deficits in antiviral immunity and have an impaired memory CD8+ CTL response.
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DOI：
10.1084/jem.183.5.2129
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发表时间：
1996-05-01
期刊：
影响因子：
--
通讯作者：
Flavell RA
中科院分区：
文献类型：
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作者：
Borrow P;Tishon A;Lee S;Xu J;Grewal IS;Oldstone MB;Flavell RA
CD40配体（CD40L）在活化的CD4+ T细胞表面表达，其在T- b细胞协同和胸腺依赖性体液免疫中的作用已得到证实。最近，通过产生cd40l敲除小鼠，我们证实了其在体液免疫中的作用，并确定了该分子在抗原特异性CD4+ T细胞体内克隆扩增中的另一个重要功能。在这里，我们通过检测CD40L缺陷小鼠感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）、皮奇德病毒或水泡性口炎病毒后的免疫反应，研究了CD40L在体内抗病毒免疫中的潜在作用。cd40l缺陷小鼠对这些病毒的体液免疫应答严重受损，尽管病毒感染的cd40l缺陷小鼠通过不依赖CD4+ T细胞的机制产生中等滴度的抗病毒IgM和一些IgG2a。相比之下，cd40l缺陷小鼠对所有三种病毒都产生强烈的初级CTL反应。然而，有趣的是，尽管cd40l缺陷小鼠在感染LCMV两个月后可以检测到记忆CTL活性，但记忆CTL反应的效率远低于野生型小鼠。总之，研究结果表明，CD40- CD40L相互作用是强抗病毒体液免疫反应所必需的，并揭示了CD40L在建立和/或维持CD8+ CTL记忆中的新作用。
The ligand for CD40 (CD40L) is expressed on the surface of activated CD4+ T cells and its role in T-B cell collaborations and thymus- dependent humoral immunity is well established. Recently, by generating CD40L-knockout mice, we have confirmed its previously described role in humoral immunity and defined another important function of this molecule in the in vivo clonal expansion of antigen-specific CD4+ T cells. Here, we investigated the potential in vivo role of CD40L in antiviral immunity by examining the immune response mounted by CD40L- deficient mice following infection with lymphocytic choriomeningitis virus (LCMV), Pichinde virus, or vesicular stomatitis virus. Humoral immune responses of CD40L-deficient mice to these viruses were severely compromised, although moderate titres of antiviral IgM and some IgG2a were produced by virus-infected CD40L-deficient mice by a CD4+ T cell- independent mechanism. By contrast, CD40L-deficient mice made strong primary CTL responses to all three viruses. Interestingly however, although memory CTL activity was detectable in CD40L-deficient mice two months after infection with LCMV, the memory CTL response was much less efficient than in wild-type mice. Together, the results show that CD40- CD40L interactions are required for strong antiviral humoral immune responses, and reveal a novel role for CD40L in the establishment and/or maintenance of CD8+ CTL memory.