AILIM/ICOS signaling induces T-cell migration/polarization of memory/effector T-cells

Int Immunol. 2004 Oct;16(10):1515-22. doi: 10.1093/intimm/dxh153. Epub 2004 Aug 31.

Abstract

AILIM/ICOS has critical roles in the regulation of T-cell differentiation and effector T-cell function in various immune responses. The counter-ligand for AILIM/ICOS, B7h, is widely expressed in not only lymphoid tissue and antigen-presenting cells, but also in fibroblast and endothelial cells in various organs. Here, we demonstrate that activated human T-cells migrate beneath TNF-alpha-treated HUVEC and display morphological polarization via AILIM/ICOS signaling. AILIM/ICOS stimulation, in the absence of antigen stimulation, also induced T-cell polarization. Importantly, AILIM/ICOS-mediated polarization was evident in CD4+CD45RO+ memory T-cells and generated Th1 cells, but not in CD4+CD45RA+ naive T-cells and generated Th2 cells. Furthermore, AILIM/ICOS signaling is involved in transendothelial migration of Th1 cells, but not Th2 cells. Our data suggest that AILIM/ICOS-B7h interactions play an important role in the endothelium in controlling the entry of memory/effector T-cells into inflamed tissues in the periphery.

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte
  • Cell Differentiation / immunology
  • Cell Movement / immunology*
  • Cell Polarity*
  • Cells, Cultured
  • Coculture Techniques
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Humans
  • Inducible T-Cell Co-Stimulator Protein
  • Lymphocyte Activation / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology*
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th2 Cells / cytology
  • Th2 Cells / immunology*

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein