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Am. J. Respir. Cell Mol. Biol., Volume 22, Number 4, April, 2000 405-411

Human Bronchial Intraepithelial T Lymphocytes as a Distinct T-Cell Subset
Their Long-Term Survival in SCID-Hu Chimeras

Eisuke Goto, Hirotsugu Kohrogi, Naomi Hirata, Kaori Tsumori, Susumu Hirosako, Junji Hamamoto, Kazuhiko Fujii, Osamu Kawano, and Masayuki Ando

First Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan

Intestinal intraepithelial T lymphocytes (i-IELs) show features different from those of conventional T cells and play specific roles in the mucosal immunity. To investigate whether human bronchial intraepithelial T lymphocytes (IELs) are a distinct entity, we examined T cells in human bronchial xenografts transplanted on mice with severe combined immune deficiency (SCID). We transplanted human bronchi subcutaneously into mice with SCID, resected the xenografts after various incubation periods (7-174 d), and examined them for CD3+, CD4+, CD8+, and CD45+ cells by immunohistochemistry. The number of CD3+ cells in the lamina propria decreased significantly in the first month (from 308.7 ± 60.2 to 70.9 ± 49.4/mm2; P < 0.05), and xenografts more than 5 mo of age had scant T cells in the lamina propria (5.2 ± 2.0/mm2). However, there was no significant difference between the number of CD3+ IELs in freshly isolated bronchi and in xenografts maintained for more than 5 mo. In freshly isolated bronchi, the number of CD4+ IELs was significantly lower than that of CD8+ cells (2.35 ± 0.62 versus 4.56 ± 1.32/mm basement membrane; P < 0.01). After transplantation, the mean CD4-to-CD8 ratio of all xenografts was significantly higher than that of freshly isolated bronchi (5.2 ± 0.9 versus 0.6 ± 0.2; P < 0.005). The IELs were positive for CD45, which is specific for human leukocytes, and they were eliminated by irradiation before the transplantation. Almost all IELs (99.5%) in the xenografts expressed alpha beta T-cell receptor, and 35.8% of IELs expressed alpha ebeta 7 integrin. Bronchial epithelial cells in the xenografts expressed interleukin (IL)-7, stem cell factor, intercellular adhesion molecule (ICAM)-1, and human leukocyte antigen-DR (HLA-DR). We conclude that in the SCID-Hu chimera model, human bronchial IELs survive for more than 5 mo, unlike the T cells in the lamina propria, and we suggest that human bronchial IELs may be stimulated by bronchial epithelial cells expressing IL-7, stem cell factor, ICAM-1, and HLA-DR.




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