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

Reina E. Mebius, Philip Streeter, Sara Michie, Eugene C. Butcher, Irving L. Weissman

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

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 α4β7 on circulating cells. Before birth, 40-70% of peripheral blood leukocytes are L-selectin-positive, while only 1-2% expresses α4β7. However, the fetal lymph nodes preferentially attract α4β7-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 α4β7 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.

Original languageEnglish (US)
Pages (from-to)11019-11024
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number20
DOIs
StatePublished - Oct 1 1996
Externally publishedYes

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Lymphocyte Homing Receptors
Venules
Lymph Nodes
Lymphocytes
L-Selectin
Parturition
Peyer's Patches
Integrins
Leukocytes
L-selectin counter-receptors
Antibodies
Population

Keywords

  • lymphocyte migration
  • MAdCAM-1
  • ontogeny

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A developmental switch in lymphocyte homing receptor and endothelial vascular addressin expression regulates lymphocyte homing and permits CD4+CD3- cells to colonize lymph nodes. / Mebius, Reina E.; Streeter, Philip; Michie, Sara; Butcher, Eugene C.; Weissman, Irving L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 20, 01.10.1996, p. 11019-11024.

Research output: Contribution to journalArticle

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