T lymphocytes negatively regulate lymph node lymphatic vessel formation

Immunity. 2011 Jan 28;34(1):96-107. doi: 10.1016/j.immuni.2010.12.016. Epub 2011 Jan 20.

Abstract

Lymph node lymphatic vessels (LNLVs) serve as a conduit to drain antigens from peripheral tissues to within the lymph nodes. LNLV density is known to be positively regulated by vascular endothelial growth factors secreted by B cells, macrophages, and dendritic cells (DCs). Here, we show that LNLV formation was negatively regulated by T cells. In both steady and inflammatory states, the density of LNLVs was increased in the absence of T cells but decreased when T cells were restored. Interferon-γ secretion by T cells suppressed lymphatic-specific genes in lymphatic endothelial cells and consequently caused marked reduction in LNLV formation. When T cells were depleted, recruitment of antigen-carrying DCs to LNs was augmented, reflecting a compensatory mechanism for antigen presentation to T cells through increased LNLVs. Thus, T cells maintain the homeostatic balance of LNLV density through a negative paracrine action of interferon-γ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Cell Movement / genetics
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Endothelium, Lymphatic / immunology
  • Endothelium, Lymphatic / metabolism*
  • Endothelium, Lymphatic / pathology
  • Feedback, Physiological
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism*
  • Lymph Nodes / pathology
  • Lymphangiogenesis / genetics
  • Lymphatic Vessels / metabolism
  • Lymphatic Vessels / pathology*
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Paracrine Communication / genetics
  • Paracrine Communication / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Interferon-gamma