MHC class II engagement by its ligand LAG-3 (CD223) leads to a distinct pattern of chemokine and chemokine receptor expression by human dendritic cells

Vaccine. 2003 Feb 14;21(9-10):862-8. doi: 10.1016/s0264-410x(02)00533-9.

Abstract

Upon stimulation by infectious agent products, dendritic cells (DC) become activated, express high levels of class I and class II antigens, CD80, CD86 and CD83 and migrate to secondary lymphoid organs where they can prime naive CD4-helper and CD8-cytotoxic T-cells. Cognate CD4(+) T-cell help mediated by CD40L along with DC stimulation with another T-cell effector molecule, termed lymphocyte activated gene-3 (LAG-3 or CD223, a ligand for MHC class II) have been shown to induce this maturation process. Both CD40L and LAG-3 have been used as vaccine adjuvants to induce CTL and CD4 Th1 responses. Here, we studied the effect of a soluble LAG-3Ig molecule on the chemokine and chemokine receptor profile of human immature monocyte-derived DC. LAG-3Ig, unlike CD40L, induced an inflammatory signal in terms of IL-8 and MIP-1alpha/CCL3 production and, in contrast to LPS, induced production of chemokines (MDC/CCL22 and TARC/CCL17) known to direct the migration of maturing DC to lymph nodes. In LAG-3-matured DC, surface expression of CCR5 (a receptor for MIP-1alpha/CCL3) was down-regulated and CCR7 (a receptor for MIP-3beta and SLC) was up-regulated. However, LAG-3-matured, but not LPS- or CD40L-matured DC retained their capacity to migrate in chemotaxis chambers and to respond to MIP-1alpha. Altogether, these data represent the first evidence that MHC class II signaling may affect DC migration to secondary lymphoid tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD*
  • Cell Differentiation
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokines / metabolism*
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology
  • Gene Expression
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • In Vitro Techniques
  • Ligands
  • Macrophage Inflammatory Proteins / pharmacology
  • Membrane Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CCR5 / genetics
  • Receptors, CCR7
  • Receptors, Chemokine / genetics*

Substances

  • Antigens, CD
  • CCR7 protein, human
  • CD223 antigen
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokines
  • Histocompatibility Antigens Class II
  • Ligands
  • Macrophage Inflammatory Proteins
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, CCR5
  • Receptors, CCR7
  • Receptors, Chemokine