A developmental switch in lymphocyte homing receptor and endothelial vascular addressin expression regulates lymphocyte homing and permits CD4+ CD3- cells to colonize lymph nodes.
IN adult mice, the dominant adhesion molecules involved in homing to lymph nodes are L-selectin homing receptors on lymphocytes and the peripheral lymph node addressins on specialized high endothelial venules. Here we show that, from fetal life through the first 24 hr of life, the dominant adhesion molecules are the mucosal addressin MAdCAM-1 on lymph node high endothelial venules and its counterreceptor, the Peyer's patch homing receptor, integrin alpha 4 beta 7 on circulating cells. Before birth, 40-70% of peripheral blood leukocytes are L-selectin-positive, while only 1-2% expresses alpha 4 beta 7. However, the fetal lymph nodes preferentially attract alpha 4 beta 7-expressing cells, and this can be blocked by fetal administration of anti-MAdCAM-1 antibodies. During fetal and early neonatal life, when only MAdCAM-1 is expressed on high endothelial venules, an unusual subset of CD4 + CD3- cells, exclusively expressing alpha 4 beta 7 as homing receptors, enters the lymph nodes. Beginning 24 hr after birth a developmental switch occurs, and the peripheral node addressins are upregulated on high endothelial venules in peripheral and mesenteric lymph nodes. This switch in addressin expression facilitates tissue-selective lymphocyte migration and mediates a sequential entry of different cell populations into the lymph nodes.
Mebius
R E
RE
Department of Pathology, Stanford University School of Medicine, CA 94305, USA.
Streeter
P R
PR
Michie
S
S
Butcher
E C
EC
Weissman
I L
IL
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D015815:Cell Adhesion Molecules; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D007136:Immunoglobulins / Q000378:metabolism*; D039441:Integrin alpha4; D039641:Integrin beta Chains; D016023:Integrins / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000196:embryology*; D016131:Lymphocyte Subsets / Q000378:metabolism; D008221:Lymphoid Tissue / Q000196:embryology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009088:Mucoproteins / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D014018:Tissue Distribution
D015703:Antigens, CD; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039641:Integrin beta Chains; D016023:Integrins; C069886:L-selectin counter-receptors; C489082:Madcam1 protein, mouse; D008565:Membrane Proteins; D009088:Mucoproteins; D016201:Receptors, Lymphocyte Homing; C091368:integrin beta7; D019041:L-Selectin; D039441:Integrin alpha4