E. Goto et al., Human bronchial intraepithelial T lymphocytes as a distinct T-cell subset - Their long-term survival in SCID-Hu chimeras, AM J RESP C, 22(4), 2000, pp. 405-411
Citations number
42
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Intestinal intraepithelial T lymphocytes (i-IELs) show features different f
rom those of conventional T cells and play specific roles in the mucosal im
munity. To investigate whether human bronchial intraepithelial T lymphocyte
s (IELs) are a distinct entity, we examined T cells in human bronchial xeno
grafts 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 the
m for CD3(+), CD4(+), CD8(+), and CD45(+) cells by immunohistochemistry. Th
e number of CD3(+) cells in the lamina propria decreased significantly in t
he 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 th
e number of CD3(+) IEL5 in freshly isolated bronchi and in xenografts maint
ained 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 vers
us 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 t
hey were eliminated by irradiation before the transplantation. Almost all I
ELs (99.5%) in the xenografts expressed alpha beta T-cell receptor, and 35.
8% of IELs expressed alpha e beta 7 integrin. Bronchial epithelial cells in
the xenografts expressed interleukin (IL)-7, stem cell factor, intercellul
ar adhesion molecule (ICAM)-1, and human leukocyte antigen-DR (HLA-DR). We
conclude that in the SCID-Hu chimera model, human bronchial IELs survive fo
r 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 e
xpressing IL-7, stem cell factor, ICAM-1, and HLA-DR.