Artificial lymph nodes induce potent secondary immune responses in naive and immunodeficient mice
Artificial lymph nodes induce potent secondary immune responses in naive and immunodeficient mice
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DOI：
10.1172/jci30379
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发表时间：
2007-04-01
影响因子：
15.9
通讯作者：
Watanabe, Takeshi
中科院分区：
文献类型：
--
作者：
Okamoto, Noriaki;Chihara, Risa;Watanabe, Takeshi
我们以前证明，人工淋巴结（aLN）可以产生在小鼠的植入基质细胞包埋的生物相容性支架到他们的肾包膜下空间。在aLN中形成的T和B细胞结构域具有与正常淋巴组织的滤泡相似的免疫应答功能。在本研究中，我们表明aLN可以移植到正常小鼠和SCID小鼠身上，它们可以有效地诱导二次免疫反应。抗原特异性二次反应强烈诱导aLN，甚至4周后移植。接受移植aLN的淋巴细胞缺陷型SCID小鼠中的抗原特异性抗体应答是实质性的。来自aLN的细胞迁移到SCID小鼠脾脏和BM，在那里它们扩增以产生大量抗原特异性抗体形成细胞。在免疫后随时间维持次级应答（即，抗原攻击），表明aLN可以支持记忆B细胞和长寿浆细胞的发育。记忆性CD4（+）T细胞在aLN移植的SCID小鼠的aLN和脾脏中富集。我们的研究结果表明，aLN在免疫缺陷小鼠中支持强的抗原特异性二次抗体应答，并提示未来临床应用的可能性。
We previously demonstrated that artificial lymph nodes (aLNs) could be generated in mice by the implantation of stromal cell-embedded biocompatible scaffolds into their renal subcapsular spaces. T and B cell domains that form in aLNs have immune response functions similar to those of follicles of normal lymphoid tissue. In the present study, we show that the aLNs were transplantable to normal as well as SCID mice, where they efficiently induced secondary immune responses. Antigen-specific secondary responses were strongly induced in aLNs even 4 weeks after their transplantation. The antigen-specific antibody responses in lymphocyte-deficient SCID mice receiving transplanted aLNs were substantial. The cells from the aLNs migrated to the SCID mouse spleen and BM, where they expanded to generate large numbers of antigen-specific antibody-forming cells. Secondary responses were maintained over time after immunization (i.e., antigen challenge), indicating that aLNs can support the development of memory B cells and long-lived plasma cells. Memory CD4(+) T cells were enriched in the aLNs and spleens of aLN-transplanted SCID mice. Our results indicate that aLNs support strong antigen-specific secondary antibody responses in immunodeficient mice and suggest the possibility of future clinical applications.