Heritage P L, Underdown B J, Arsenault A L, Snider D P, McDermott M R
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Am J Respir Crit Care Med. 1997 Oct;156(4 Pt 1):1256-62. doi: 10.1164/ajrccm.156.4.97-03017.
The nasal mucosal is the first site of contact with inhaled antigens. However, the nature of local immune responses and the role of nasal-associated lymphoid tissue (NALT) in those responses have rarely been studied. To characterize the cells involved in mucosally derived immune responses, NALT and Peyer's patch (PP) cells from normal mice, and mice immunized intragastrically or intranasally with cholera toxin (CT), were isolated and analyzed. Compared with PP cells, unstimulated NALT cells contained a higher proportion of T-cells. The CD4:CD8 ratio in NALT cell preparations was less than that observed in PP and more closely resembled that seen in spleen. Additionally, the total B-cell frequency in NALT cell isolates was 20% lower than that observed in PP cell preparations. Although NALT and PP cell isolates contained both mature B-cells and cells undergoing activation to express surface IgA, unlike PP, NALT showed no significant frequency of IgA-switched cells. After intranasal immunization with CT, toxin-specific IgA antibody-forming cells (AFCs) were detected in NALT cell preparations. The numbers of these cells correlated with CT-specific IgA in nasal, but not in gut washes or sera, thus suggesting local nasal production of antigen-specific mucosal antibodies. There was no evidence of anti-CT AFCs in NALT or CT-specific antibody in nasal washes after intragastric CT administration. These results support the notion that nasal mucosal antibody production is best achieved via direct stimulation of IgA-committed, NALT-derived B-cells.
鼻黏膜是与吸入抗原接触的首个部位。然而,局部免疫反应的性质以及鼻相关淋巴组织(NALT)在这些反应中的作用鲜有研究。为了表征参与黏膜源性免疫反应的细胞,从正常小鼠以及经胃内或鼻内用霍乱毒素(CT)免疫的小鼠中分离并分析了NALT和派尔集合淋巴结(PP)细胞。与PP细胞相比,未受刺激的NALT细胞含有更高比例的T细胞。NALT细胞制剂中的CD4:CD8比率低于PP中观察到的比率,且更类似于脾脏中的比率。此外,NALT细胞分离物中的总B细胞频率比PP细胞制剂中观察到的低20%。尽管NALT和PP细胞分离物中都含有成熟B细胞和正在被激活以表达表面IgA的细胞,但与PP不同,NALT中未观察到明显频率的IgA转换细胞。经鼻内用CT免疫后,在NALT细胞制剂中检测到毒素特异性IgA抗体形成细胞(AFC)。这些细胞的数量与鼻腔中而非肠道冲洗液或血清中的CT特异性IgA相关,因此提示鼻腔局部产生抗原特异性黏膜抗体。胃内给予CT后,NALT中没有抗CT AFC的证据,鼻腔冲洗液中也没有CT特异性抗体。这些结果支持这样一种观点,即通过直接刺激源自NALT的IgA定向B细胞能最佳地实现鼻黏膜抗体产生。