A developmental switch in lymphocyte homing receptor and endothelial vascular addressin expression regulates lymphocyte homing and permits CD4+CD3- cells to colonize lymph nodes

被引:199
作者
Mebius, RE
Streeter, PR
Michie, S
Butcher, EC
Weissman, IL
机构
[1] STANFORD UNIV,SCH MED,DEPT PATHOL,STANFORD,CA 94305
[2] STANFORD UNIV,SCH MED,DEPT DEV BIOL,STANFORD,CA 94305
[3] MONSANTO CO,DEPT IMMUNOL,ST LOUIS,MO 63198
[4] VET AFFAIRS HLTH CARE SYST,CTR MOL BIOL MED,PALO ALTO,CA 94304
关键词
ontogeny; MAdCAM-1; lymphocyte migration;
D O I
10.1073/pnas.93.20.11019
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:11019 / 11024
页数:6
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