Chentoufi Aziz Alami, Dasgupta Gargi, Nesburn Anthony B, Bettahi Ilham, Binder Nicholas R, Choudhury Zareen S, Chamberlain Winston D, Wechsler Steven L, BenMohamed Lbachir
Laboratory of Cellular and Molecular Immunology, University of California, Irvine, Medical Center, Orange, CA 92868, USA.
Clin Vaccine Immunol. 2010 Mar;17(3):342-53. doi: 10.1128/CVI.00347-09. Epub 2010 Jan 20.
Both topical ocular and topical intranasal immunizations have been reported to stimulate the ocular mucosal immune system (OMIS) and the systemic immune system. Nasolacrimal ducts (NLDs) are the connecting bridges between the OMIS and nasal cavity-associated lymphoid tissue (NALT). These ducts drain topical ocularly administrated solutions into the inferior meatus of the nose to reach the NALT. Inversely, NLDs also drain intranasally administrated solutions to the mucosal surface of the eye and thus the OMIS. This unique anatomical connection between the OMIS and NALT systems provoked us to test whether the OMIS and NALT are immunologically interdependent. In this report, we show that both topical ocular administration and topical intranasal administration of a mixture of immunodominant CD4(+) T-cell epitope peptides from herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) emulsified with the CpG(2007) mucosal adjuvant are capable of inducing local (in conjunctiva) as well as systemic (in spleen) HSV-peptide-specific CD4(+) T-cell responses. Interestingly, surgical closure of NLDs did not significantly alter local ocular mucosal CD4(+) T-cell responses induced following topical ocular immunization but did significantly enhance systemic CD4(+) T-cell responses (as measured by both T-cell proliferation and gamma interferon (IFN-gamma) production; P < 0.005). In contrast, NLD closure significantly decreased ocular mucosal, but not systemic, CD4(+) T-cell responses following intranasal administration of the same vaccine solution (P < 0.001). The study suggests that NALT and the OMIS are immunologically interconnected.
据报道，眼部局部免疫和鼻内局部免疫均可刺激眼部黏膜免疫系统（OMIS）和全身免疫系统。鼻泪管（NLDs）是OMIS与鼻腔相关淋巴组织（NALT）之间的连接桥梁。这些管道将眼部局部给药的溶液引流至鼻下鼻道，从而到达NALT。相反，NLDs也将鼻内给药的溶液引流至眼黏膜表面，进而到达OMIS。OMIS和NALT系统之间这种独特的解剖学联系促使我们测试OMIS和NALT在免疫方面是否相互依存。在本报告中，我们表明，用CpG(2007)黏膜佐剂乳化的单纯疱疹病毒1型（HSV-1）糖蛋白D（gD）的免疫显性CD4(+) T细胞表位肽混合物进行眼部局部给药和鼻内局部给药，均能够诱导局部（结膜）以及全身（脾脏）的HSV肽特异性CD4(+) T细胞反应。有趣的是，手术封闭NLDs并没有显著改变眼部局部免疫后诱导的局部眼部黏膜CD4(+) T细胞反应，但确实显著增强了全身CD4(+) T细胞反应（通过T细胞增殖和γ干扰素（IFN-γ）产生来衡量；P < 0.005）。相反，在鼻内给予相同疫苗溶液后，封闭NLDs显著降低了眼部黏膜CD4(+) T细胞反应，但对全身CD4(+) T细胞反应没有影响（P < 0.001）。该研究表明，NALT和OMIS在免疫方面相互关联。
