Essential role of lymph nodes in contact hypersensitivity revealed in lymphotoxin-α-deficient mice

Paul D. Rennert, Paula S. Hochman, Richard A. Flavell, David D. Chaplin, Sundararajan Jayaraman, Jeffrey L. Browning, Yang Xin Fu

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Lymph nodes (LNs) are important sentinal organs, populated by circulating lymphocytes and antigen-bearing cells exiting the tissue beds. Although cellular and humoral immune responses are induced in LNs by antigenic challenge, it is not known if LNs are essential for acquired immunity. We examined immune responses in mice that lack LNs due to genetic deletion of lymphotoxin ligands or in utero blockade of membrane lymphotoxin. We report that LNs are absolutely required for generating contact hypersensitivity, a T cell-dependent cellular immune response induced by epicutaneous hapten. We show that the homing of epidermal Langerhans cells in response to hapten application is specifically directed to LNs, providing a cellular basis for this unique LN function. In contrast, the spleen cannot mediate contact hypersensitivity because antigen-bearing epidermal Langerhans cells do not access splenic white pulp. Finally, we formally demonstrate that LNs provide a unique environment essential for generating this acquired immune response by reversing the LN defect in lymphotoxin-α-/- mice, thereby restoring the capacity for contact hypersensitivity.

Original languageEnglish (US)
Pages (from-to)1227-1238
Number of pages12
JournalJournal of Experimental Medicine
Volume193
Issue number11
DOIs
StatePublished - Jun 4 2001

Keywords

  • Antigens
  • Haptens
  • Langerhans cells
  • Lymphoid tissue
  • Spleen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Rennert, P. D., Hochman, P. S., Flavell, R. A., Chaplin, D. D., Jayaraman, S., Browning, J. L., & Fu, Y. X. (2001). Essential role of lymph nodes in contact hypersensitivity revealed in lymphotoxin-α-deficient mice. Journal of Experimental Medicine, 193(11), 1227-1238. https://doi.org/10.1084/jem.193.11.1227