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

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 rst 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 a4(87 on circulating cells. Before birth, 40-70%o of peripheral blood leukocytes are L-selectin-positive, while only 1-2% expresses a4,B7. However, the fetal lymph nodes preferentially attract a487-expressing cells, and this can be blocked by fetal administration of anti- 4).The primary adhesion molecules are involved in initial "rolling" contacts, to be followed by secondary adhesive events required for arrest and subsequent transendothelial migration of these cells (5-7). To enter an adult peripheral LN (PLN), lymphocytes express high levels of the homing receptor Lselectin (8)(9)(10)(11) 11019The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Absence of Nkx2-3 Homeodomain Transcription Factor Reprograms the Endothelial Addressin Preference for Lymphocyte Homing in Peyer’s Patches

“…In this process members of the TNF/LT induce the expression of stromal and endothelial MAdCAM-1, which is required for the initial recruitment of lymphocytes to the forming PP anlage (29,30). In Nkx2-3 2/2 mice MAdCAM-1 expression is preserved in PPs until the perinatal period, in agreement with previous data demonstrating HEV-associated MAdCAM-1 in neonatal mLNs (17).…”

“…The MAdCAM-1 to PNAd switch in HEVs of mutant PPs resembles the physiological switch in pLNs of wild-type mice during the first weeks of life in which Nkx2-3 is not appreciably expressed (29). This suggests that Nkx2-3 functions as a repressor of the MAdCAM-1 to PNAd exchange.…”

“…Previous data on the maturation of HEVs indicated that postnatally HEVs in murine pLNs display MAdCAM-1, which is gradually replaced by PNAd during the first postnatal month (29). This process coincides with the colonization of developing LNs with T and B lymphocytes, and it requires signaling through LTbR expressed on endothelial cells (30,31).…”

How One Thing Led to Another

“…They were the first described innate lymphoid cells; our subset functioned to establish HEVs, as well as to induce the structural domains in lymph nodes and Peyer patches (79,80). These cells are present in fetal mice, but we could not see them in adults.…”

“…These cells are present in fetal mice, but we could not see them in adults. Amazingly, we found that they gained access to incipient lymph nodes that expressed the Peyer patch addressin MAdCAM-1 rather than the lymph node addressin PNAd; the HEVs then switched soon after birth to their normal addressin expression for life, after lymph node architecture was established (79,81,82).…”