Human bronchial intraepithelial T lymphocytes as a distinct T-cell subset: their long-term survival in SCID-Hu chimeras.
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/mm(2); P < 0.05), and xenografts more than 5 mo of age had scant T cells in the lamina propria (5.2 +/- 2.0/mm(2)). 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 alphabeta T-cell receptor, and 35.8% of IELs expressed alpha(e)beta7 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.
Goto
E
E
First Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan.
Kohrogi
H
H
Hirata
N
N
Tsumori
K
K
Hirosako
S
S
Hamamoto
J
J
Fujii
K
K
Kawano
O
O
Ando
M
M
D000818:Animals; D015415:Biomarkers; D001980:Bronchi / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D019070:Cell Lineage; D002470:Cell Survival; D002678:Chimera; D004848:Epithelium / Q000276:immunology; D006085:Graft Survival; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016023:Integrins / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D015851:Interleukin-7 / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008168:Lung / Q000166:cytology* / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D016513:Mice, SCID; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D019089:Stem Cell Factor / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000528:radiation effects; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic
D015415:Biomarkers; D006684:HLA-DR Antigens; D016023:Integrins; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D019089:Stem Cell Factor; C070709:integrin alphaEbeta7; D018799:Intercellular Adhesion Molecule-1; D017493:Leukocyte Common Antigens