Tsumori Kaori, Kohrogi Hirotsugu, Goto Eisuke, Hirata Naomi, Hirosako Susumu, Fujii Kazuhiko, Ando Makoto, Kawano Osamu, Mizuta Hiroshi
First Department of Internal Medicine, Kumamoto University School of Medicine, Honjo, Kumamoto, Japan.
J Immunol. 2003 Jun 1;170(11):5712-8. doi: 10.4049/jimmunol.170.11.5712.
T cells play an important role in the pathogenesis of bronchial asthma. However, it is not completely known how circulating lymphocytes infiltrate into the airways of asthmatic patients. Because SCID mice are unable to reject xenogenic transplants, many xenotransplant models using various human tissues have been developed. Therefore, to examine the interaction between bronchi and T lymphocytes of asthma, it may be possible to use the human bronchial xenograft and PBMC xenograft in SCID mice. We transplanted human bronchi into the subcutaneum of SCID mice and i.p. injected PBMCs that were obtained from patients with atopic asthma, atopic dermatitis and rheumatoid arthritis, and normal subjects (asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice). There was no difference in the percentage of CD3-, CD4-, CD8-, CD25-, CD45RO-, CD103-, and cutaneous lymphocyte Ag-positive cells in PBMCs among the patients with asthma, dermatitis, rheumatoid arthritis, and normal subjects, and CD3-positive cells in peripheral blood of asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice. The number of CD3-, CD4-, and CD8-positive cells in the xenografts of asthmatic huPBMC-SCID mice was higher than those of dermatitis, rheumatic, and normal huPBMC-SCID mice. IL-4 mRNA and IL-5 mRNA were significantly higher in the xenografts of asthmatic huPBMC-SCID mice than those in the xenografts of normal huPBMC-SCID mice, but there were no significant differences in the expressions of IL-2 mRNA or IFN-gamma mRNA between them. These findings suggest that T cells, especially Th2-type T cells, of asthmatics preferentially infiltrate into the human bronchi.
T细胞在支气管哮喘的发病机制中起重要作用。然而,循环淋巴细胞如何浸润到哮喘患者气道中尚不完全清楚。由于重症联合免疫缺陷(SCID)小鼠无法排斥异种移植,因此已开发出许多使用各种人体组织的异种移植模型。因此,为了研究哮喘患者支气管与T淋巴细胞之间的相互作用,有可能在SCID小鼠中使用人支气管异种移植和外周血单核细胞(PBMC)异种移植。我们将人支气管移植到SCID小鼠皮下,并腹腔注射从特应性哮喘、特应性皮炎、类风湿关节炎患者及正常受试者获取的PBMC(哮喘、皮炎、风湿和正常huPBMC-SCID小鼠)。哮喘、皮炎、类风湿关节炎患者及正常受试者的PBMC中CD3、CD4、CD8、CD25、CD45RO、CD103及皮肤淋巴细胞抗原阳性细胞的百分比,以及哮喘、皮炎、风湿和正常huPBMC-SCID小鼠外周血中CD3阳性细胞无差异。哮喘huPBMC-SCID小鼠异种移植中CD3、CD4和CD8阳性细胞数量高于皮炎、风湿和正常huPBMC-SCID小鼠。哮喘huPBMC-SCID小鼠异种移植中IL-4 mRNA和IL-5 mRNA显著高于正常huPBMC-SCID小鼠异种移植,但它们之间IL-2 mRNA或IFN-γ mRNA表达无显著差异。这些发现表明,哮喘患者的T细胞,尤其是Th2型T细胞,优先浸润到人支气管中。