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PMID: 11390430 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of experimental medicine ·Vol. 193 ·No. 11 ·2001-06-04 ·Pages 1227-38

Rennert PD, Hochman PS, Flavell RA, Chaplin DD, Jayaraman S, Browning JL, Fu YX

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-alpha(-/)- mice, thereby restoring the capacity for contact hypersensitivity.

MeSH Terms
Animals Cell Movement Dendritic Cells/physiology Dermatitis, Contact/etiology Female Langerhans Cells/physiology Lymph Nodes/physiology Lymphotoxin-alpha/physiology Lymphotoxin-beta Membrane Proteins/physiology Mice Mice, Inbred BALB C Mice, Inbred C3H
Chemicals
Ltb protein, mouse Lymphotoxin-alpha Lymphotoxin-beta Membrane Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Rennert P D
Department of Immunology and Inflammation, Biogen, Incorporated, 14 Cambridge Center, Cambridge, MA 02142, USA. paul_rennert@biogen.com
Hochman P S
Flavell R A
Chaplin D D
Jayaraman S
Browning J L
Fu Y X
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.193.11.1227
Email
paul_rennert@biogen.com
Published
2001-06-04
Pages
1227-38
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193379
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.193.11.1227 PMC Full Text View journal details
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