Protective mucosal immunity in aging is associated with functional CD4+ T cells in nasopharyngeal-associated lymphoreticular tissue
Protective mucosal immunity in aging is associated with functional CD4+ T cells in nasopharyngeal-associated lymphoreticular tissue
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DOI：
10.4049/jimmunol.170.4.1754
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发表时间：
2003-02-15
影响因子：
4.4
通讯作者：
Fujihashi, K
中科院分区：
文献类型：
--
作者：
Hagiwara, Y;McGhee, JR;Fujihashi, K
我们以前的研究表明，粘膜免疫受损的1岁小鼠，已口服免疫与卵蛋白和天然霍乱毒素（nCT）作为粘膜佐剂。在这项研究中，我们询问是否类似的免疫失调也存在于鼻腔免疫小鼠的粘膜隔室。1岁和年轻的成年小鼠每周用三次鼻腔剂量的OVA和nCT或用来自短芽孢杆菌的无毒嵌合肠毒素（天然不稳定毒素的突变霍乱毒素-A E112 K/B亚基）免疫。在给予nCT或嵌合肠毒素作为粘膜佐剂的年轻成年小鼠和1岁小鼠中，均观察到血浆中OVA特异性IgG抗体和粘膜分泌物（鼻洗液、唾液和粪便提取物）中分泌型伊加抗体水平升高。在1岁小鼠的颈部淋巴结和脾脏中观察到显著水平的OVA特异性CD 4（+）T细胞增殖和OVA诱导的Th 1和Th 2型细胞因子应答。在这方面，在1岁小鼠的鼻咽相关淋巴网状组织中检测到的CD 4（+）、CD 45 RB（+）T细胞数量多于年轻成年小鼠，但在派尔集合淋巴结或脾脏中则没有发现同样的情况。一岁大的小鼠给予鼻破伤风类毒素加上嵌合毒素作为佐剂，保护免受破伤风毒素的致命攻击。这一结果加强了我们的发现，即年龄相关的免疫改变首先发生在肠道相关的淋巴网状组织，因此鼻咽相关的淋巴网状组织为基础的粘膜免疫疫苗的鼻腔递送提供了一个有吸引力的可能性，以保护老年人。免疫学杂志，2003年。
Our previous studies showed that mucosal immunity was impaired in 1-year-old mice that had been orally immunized with OVA and native cholera toxin (nCT) as mucosal adjuvant. In this study, we queried whether similar immune dysregulation was also present in mucosal compartments of mice immunized by the nasal route. Both 1-year-old and young adult mice were immunized weekly with three nasal doses of OVA and nCT or with a nontoxic chimeric enterotoxin (mutant cholera toxin-A E112K/B subunit of native labile toxin) from Brevibacillus choshinensis. Elevated levels of OVA-specific IgG Abs in plasma and secretory IgA Abs in mucosal secretions (nasal washes, saliva, and fecal extracts) were noted in both young adult and 1-year-old mice given nCT or chimeric enterotoxin as mucosal adjuvants. Significant levels of OVA-specific CD4(+) T cell proliferative and OVA-induced Th1-and Th2-type cytokine responses were noted in cervical lymph nodes and spleen of 1-year-old mice. In this regard, CD4(+), CD45RB(+) T cells were detected in greater numbers in the nasopharyngeal-associated lymphoreticular tissues of 1-year-old mice than of young adult mice, but the same did not hold true for Peyer's patches or spleen. One-year-old mice given nasal tetanus toxoid plus the chimeric toxin as adjuvant were protected from lethal challenge with tetanus toxin. This result reinforced our findings that age-associated immune alterations occur first in gut-associated lymphoreticular tissues, and thus nasal delivery of vaccines for nasopharyngeal-associated lymphoreticular tissue-based mucosal immunity offers an attractive possibility to protect the elderly. The Journal of Immunology, 2003.