Nasal-associated lymphoid tissue is a mucosal inductive site for virus-specific humoral and cellular immune responses

Nasal-associated lymphoid tissue is a mucosal inductive site for virus-specific humoral and cellular immune responses
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DOI:
10.4049/jimmunol.168.4.1796
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发表时间:
2002-02-15
影响因子:
4.4
通讯作者:
Cebra, JJ
Cebra, JJ
中科院分区:
医学2区
文献类型:
--
作者:
Zuercher, AW;Coffin, SE;Cebra, JJ

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派尔集合淋巴结是胃肠道中体液和细胞免疫应答的粘膜诱导部位。相比之下,呼吸道中的功能等同结构仍然难以捉摸。鼻相关淋巴组织(NALT)可能是上呼吸道的粘膜诱导部位。然而,粘膜诱导位点的典型体征,如Ag刺激后生发中心反应的发展和幼稚B细胞向伊加产生的同种型转换,尚未得到直接证实。此外,还不知道CTL是否可以在NALT中生成。为了解决这些问题,使用呼肠孤病毒鼻内感染C3H小鼠的模型对NALT进行结构和功能分析。FACS和组织学分析显示NALT中生发中心的发育与鼻内呼肠孤病毒感染后伊加(+)和IgG 2a(+)B细胞的产生和扩增平行。呼肠孤病毒特异性伊加产生于上呼吸道和胃肠道,而呼肠孤病毒特异性IgG2a的产生仅限于NALT、下颌下和肠系膜淋巴结。此外,在NALT中检测到病毒特异性CTL。有限稀释分析显示,与颈部淋巴结相比,NALT中的前体CTL频率高5至6倍。这些数据一起提供了直接证据,表明NALT是上呼吸道体液和细胞免疫应答的粘膜诱导位点。
Peyer's patches are known as mucosal inductive sites for humoral and cellular immune responses in the gastrointestinal tract. In contrast, functionally equivalent structures in the respiratory tract remain elusive. It has been suggested that nasal-associated lymphoid tissue (NALT) might serve as a mucosal inductive site in the upper respiratory tract. However, typical signs of mucosal inductive sites like development of germinal center reactions after Ag stimulation and isotype switching of naive B cells to IgA production have not been directly demonstrated. Moreover, it is not known whether CTL can be generated in NALT. To address these issues, NALT was structurally and functionally analyzed using a model of intranasal infection of C3H mice with reovirus. FACS and histological analyses revealed development of germinal centers in NALT in parallel with generation and expansion of IgA(+) and IgG2a(+) B cells after intranasal reovirus infection. Reovirus-specific IgA was produced in both the upper respiratory and the gastrointestinal tract, whereas production of reovirus-specific IgG2a was restricted to NALT, submandibular, and mesenteric lymph nodes. Moreover, virus-specific CTL were detected in NALT. Limiting dilution analysis showed a 5- to 6-fold higher precursor CTL frequency in NALT compared with a cervical lymph node. Together these data provide direct evidence that NALT is a mucosal inductive site for humoral and cellular immune responses in the upper respiratory tract.