Heritage P L, Brook M A, Underdown B J, McDermott M R
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Immunology. 1998 Feb;93(2):249-56. doi: 10.1046/j.1365-2567.1998.00420.x.
Waldeyer's ring is located at the juncture of the respiratory and alimentary tracts, where it is bombarded by inhaled and ingested antigens. However, knowledge of its exact function or consequences of its removal is incomplete. Recently, the murine nasal-associated lymphoid tissue (NALT) has been reported to have functional similarities to Waldeyer's ring and, thus, might be a suitable model to examine the function of oronasopharyngeal lymphoid tissues. To explore the capability of NALT to incite local mucosal and systemic immunity, we immunized mice intranasally (i.n.) with 3-(triethoxysilyl)-propyl-terminated polydimethylsiloxane (TS-PDMS)-grafted microparticles (MP), an inoculant previously shown to induce robust systemic and mucosal humoral immunity following intragastric (i.g.) administration. We demonstrated that i.n. immunization with low doses of microentrapped, but not soluble, human serum albumin (HSA) evoked robust circulating IgG responses (P < 0.05). Additionally, NALT cells isolated from MP-treated mice proliferated in vitro when restimulated with HSA (P < 0.05), suggesting that i.n. immunization with HSA-containing MP incited specific immunity via NALT cell activation. Coinciding with these observations, after i.n. MP administration HSA-specific spot-forming cells (SFC) were observed in NALT, and later posterior cervical lymph nodes (pCLN) and spleen (SPL), suggesting that the observed MP-induced specific systemic antibody responses emanated from the NALT. We also showed that i.n. immunization with HSA-containing TS-PDMS-grafted MP stimulated interleukin-4 (IL-4)-secreting lymphocytes in the NALT. This cytokine microenvironment was probably responsible for driving the IgG1 sera response observed after i.n. MP administration, via the migration of NALT-derived IgG1-committed B cells. Interestingly, unlike i.g. MP administration, i.n. immunization with HSA-containing MP did not evoke detectable specific IgA in any lymphoid tissue examined, or in nasal secretions, probably reflecting differences between NALT and other mucosae-associated lymphoid tissues (MALT).
瓦尔代尔环位于呼吸道和消化道的交界处，此处会受到吸入和摄入抗原的冲击。然而，关于其确切功能或切除后果的了解并不完整。最近，有报道称小鼠鼻相关淋巴组织（NALT）与瓦尔代尔环具有功能相似性，因此可能是研究口鼻咽淋巴组织功能的合适模型。为了探究NALT激发局部黏膜和全身免疫的能力，我们用3-（三乙氧基甲硅烷基）-丙基封端的聚二甲基硅氧烷（TS-PDMS）接枝微粒（MP）经鼻内（i.n.）免疫小鼠，该接种物先前已显示在经胃内（i.g.）给药后可诱导强大的全身和黏膜体液免疫。我们证明，用低剂量微包封而非可溶性人血清白蛋白（HSA）进行鼻内免疫可引发强烈的循环IgG反应（P < 0.05）。此外，从经MP处理的小鼠中分离出的NALT细胞在用HSA再次刺激时在体外增殖（P < 0.05），这表明用含HSA的MP进行鼻内免疫通过NALT细胞活化激发了特异性免疫。与这些观察结果一致，在经鼻内给予MP后，在NALT以及随后的颈后淋巴结（pCLN）和脾脏（SPL）中观察到了HSA特异性斑点形成细胞（SFC），这表明观察到的MP诱导的特异性全身抗体反应源自NALT。我们还表明，用含HSA的TS-PDMS接枝MP进行鼻内免疫可刺激NALT中分泌白细胞介素-4（IL-4）的淋巴细胞。这种细胞因子微环境可能是通过源自NALT的IgG1定向B细胞的迁移，导致在经鼻内给予MP后观察到的IgG1血清反应的原因。有趣的是，与经胃内给予MP不同，用含HSA的MP进行鼻内免疫在任何检查的淋巴组织或鼻分泌物中均未引发可检测到的特异性IgA，这可能反映了NALT与其他黏膜相关淋巴组织（MALT）之间的差异。
