In situ demonstration of intraepithelial lymphocyte adhesion to villus microvessels of the small intestine.
The recirculation of lymphocytes through the intestinal mucosa is important for specific immune defense, but the origin and differentiation of intraepithelial lymphocytes (IEL) are not fully understood. The present study therefore used intravital microscopy to investigate the migration of IEL to the villus mucosa and Peyer's patches of the small intestine. IEL were separated from inverted murine small intestine and mesenteric lymph node (MLN) T cells were also isolated. The adhesion of fluorescence-labeled lymphocytes to postcapillary venules (PCV) of Peyer's patches and arcade microvessels of small intestinal villi was observed after injection. In some experiments, the effect of antibodies against adhesion molecules on cell kinetics were investigated. IEL time-dependently accumulated in villus microvessels of the small intestine, whereas few MLN cells did. Few IEL adhered to the PCV of Peyer's patches. IEL were shown to express alpha(E)beta(7)-integrin but not L-selectin. The accumulation of IEL in villus archade was significantly inhibited by antibody against beta(7)-integrin or mucosal addressin cell adhesion molecules (MAdCAM)-1, but not by alpha(E)-integrin. The combined blocking of beta(7)-integrin and MAdCAM-1 further attenuated the sticking of IEL in this area, although it did not entirely block the IEL adherence. The adherence of CD4(+) or TCRalphabeta IEL to villus microvessels was significantly greater than that of CD4(-) or TCRgammadelta IEL. It was demonstrated in situ for the first time that IEL adhered selectively to the villus microvessels of the small intestine partly via beta(7) and MAdCAM-1.
Koseki
S
S
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Miura
S
S
Fujimori
H
H
Hokari
R
R
Komoto
S
S
Hara
Y
Y
Ogino
T
T
Nagata
H
H
Goto
M
M
Hachimura
S
S
Kaminogawa
S
S
Ishii
H
H
D000818:Animals; D015703:Antigens, CD; D015704:CD4 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D002465:Cell Movement; D005260:Female; D007136:Immunoglobulins; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D016023:Integrins; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D007421:Intestine, Small / Q000098:blood supply / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D008643:Mesentery / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000166:cytology / Q000276:immunology*; D009088:Mucoproteins; D010581:Peyer's Patches / Q000098:blood supply / Q000166:cytology / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016201:Receptors, Lymphocyte Homing
D015703:Antigens, CD; D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D016023:Integrins; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016201:Receptors, Lymphocyte Homing; C091367:alpha E integrins; C091368:integrin beta7