Induction of secondary and tertiary lymphoid structures in the skin

Tom Cupedo, Wendy Jansen, Georg Kraal, Reina E Mebius

Research output: Contribution to journalArticleAcademicpeer-review

116 Citations (Scopus)


During embryogenesis a developmental program leading to the formation of lymph nodes and Peyer's patches is initiated. We now show that lymph node-like structures as well as tertiary lymphoid structures can ectopically be induced by intradermal injection of newborn lymph node-derived cells. ICAM-1/VCAM-1-expressing stromal organizers, follicular dendritic cells, lymphatic endothelium, and HEVs in these structures are of donor origin, while all hematopoietic cells are host derived. Formation depends on lymphotoxin-expressing donor cells, whereas further organization requires lymphotoxin-expressing recipient cells. While induced secondary lymphoid structures develop a normal cellular architecture, the degree of organization in tertiary structures is correlated to the immune activation status of the host. These results indicate that the cellular and molecular requirements for the establishment of lymph nodes and tertiary structures are remarkably similar and that hyperactivated lymphocytes can fulfill the role of lymphoid tissue inducer cells during inflammatory responses.

Original languageEnglish
Pages (from-to)655-67
Number of pages13
Issue number5
Publication statusPublished - Nov 2004


  • Animals
  • CD40 Antigens/physiology
  • Intercellular Adhesion Molecule-1/analysis
  • Lymph Nodes/cytology
  • Lymphocytes/physiology
  • Lymphoid Tissue/cytology
  • Lymphotoxin beta Receptor
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Tumor Necrosis Factor, Type I/physiology
  • Receptors, Tumor Necrosis Factor/physiology
  • Skin/immunology
  • Vascular Cell Adhesion Molecule-1/analysis

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