Lymphotoxin plays a crucial role in the development and function of nasal-associated lymphoid tissue through regulation of chemokines and peripheral node addressin

Am J Pathol. 2005 Jan;166(1):135-46. doi: 10.1016/S0002-9440(10)62239-0.


The mechanism of nasal-associated lymphoid tissue (NALT) development is incompletely understood with regard to the roles of cytokines, chemokines, and vascular addressins. Development of the wild-type NALT continued in the immediate postnatal period with gradual increases in cellularity, compartmentalization into T- and B-cell zones, and expression of lymphotoxin (LT)-alpha, LT-beta, and lymphoid chemokines (CCL21, CCL19, CXCL13). High endothelial venules (HEVs) developed that expressed GlyCAM-1, HEC-6ST [an enzyme crucial for expression of luminal peripheral node addressin (PNAd)], and PNAd itself. LT-beta(-/-) and LT-alpha(-/-) NALTs had fewer cells than those of wild-type mice, reduced (LT-beta(-/-)) or absent (LT-alpha(-/-)) lymphoid chemokines, and no T- and B-cell compartmentalization. LT-beta(-/-) HEVs expressed only abluminal PNAd and no HEC-6ST or GlyCAM-1. LT-alpha(-/-) HEVs had no PNAd, HEC-6ST, or GlyCAM-1. Because intranasal immunization gives rise to vaginal IgA, immunization of LT-beta(-/-) mice, which retain cervical lymph nodes, might generate such a response. Intranasal immunization with ovalbumin and cholera toxin revealed lower cytokine levels in the LT-alpha(-/-) and LT-beta(-/-) NALTs, and undetectable vaginal IgA. In contrast, splenic cytokines and serum IgG titers, although reduced, were detectable. These data indicate that LT-alpha(3) and LT-alpha(1)beta(2) cooperatively contribute to NALT development and function through regulation of lymphoid chemokines and adhesion molecules; they are the first to implicate LT-alpha(1)beta(2) in GlyCAM-1 regulation in NALT HEV development.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Surface / physiology*
  • B-Lymphocytes / immunology
  • Chemokines / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation
  • Lymphoid Tissue / immunology*
  • Lymphotoxin-alpha / deficiency
  • Lymphotoxin-alpha / genetics
  • Lymphotoxin-alpha / physiology*
  • Lymphotoxin-beta
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nasal Mucosa / physiology*
  • Polymerase Chain Reaction
  • T-Lymphocytes / immunology
  • Venules / immunology
  • Venules / physiology


  • Antigens, Surface
  • Chemokines
  • L-selectin counter-receptors
  • Ltb protein, mouse
  • Lymphotoxin-alpha
  • Lymphotoxin-beta
  • Membrane Proteins