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Department of Epidemiology and Public Health and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520
The mature phenotype of peripheral lymph node (LN) high endothelial venules (HEVs), defined as MAdCAM-1lowPNAdhighLT
Rhigh HEC-6SThigh, is dependent on signaling through the lymphotoxin- receptor (LTR). Plasticity of PLN HEVs during immunization with oxazolone was apparent as a reversion to an immature phenotype (MAdCAM-1highPNAdlowLTRlow HEC-6STlow) followed by recovery to the mature phenotype. The recovery was dependent on B cells and was inhibited by LTR-Ig treatment. Concurrent with HEV reversion, at day 4 following oxazolone or OVA immunization, reduced accumulation of Evans blue dye and newly activated DCs in the draining LNs revealed a temporary afferent lymphatic vessel (LV) functional insufficiency. T cell priming to a second Ag was temporarily inhibited. At day 7, lymphangiogenesis peaked in both the skin and draining LN, and afferent LV function was restored at the same time as HEV phenotype recovery. This process was delayed in the absence of B cells. LV and HEV both express the LTR. During lymphangiogenesis in the draining LN, HEV, and LV were directly apposed; some vessels appeared to express both PNAd and LYVE-1. Pretreatment with LTR-Ig drastically reduced the number of PNAd+LYVE-1+ vessels, suggesting a reduction in LV and HEV cross-talk. The concordance in time and function and the close physical contact between LVs and HEVs in the remodeling process after immunization indicate that the two vascular systems are in synchrony and engage in cross-talk through B cells and LTR.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Anna Fuller Fund (to S.L.) and National Institutes of Health Grants CA16885 and DK57731 (to N.H.R.).
2 Address correspondence and reprint requests to Dr. Nancy H. Ruddle, P.O. Box 208034, 815 Laboratory of Epidemiology and Public Health, 60 College Street, New Haven, CT 06520-8024. E-mail address: nancy.ruddle{at}yale.edu
3 Abbreviations used in this paper: LN, lymph node; LT, lymphotoxin; PLN, peripheral LN; ILN, inguinal LN; MLN, mesenteric LN; LV, lymphatic vessel; HEV, high endothelial venule; PNAd, peripheral node addressin; OX, oxazolone; SRBC, sheep RBC; WT, wild type.
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