ICAM-3 (CD50) cross-linking augments signaling in CD3-activated peripheral human T lymphocytes

Academic Article

Abstract

  • ICAM-3 is a pan-hematopoietic, constitutive adhesion molecule. ICAM-3 binds to LFA-1 on antigen-presenting cells (APC) stabilizing the T cell-APC interaction, facilitating signaling through the CD3/TCR complex. However, recent evidence using cultured and transformed T cells suggests ICAM-3 may also function in signaling. Because ICAM-3 is constitutively expressed on resting T cells, we postulated that signaling through ICAM-3 in resting T cells represents an important costimulatory mechanism in these cells. In purified resting human T cells, cross-linking both ICAM-3 and CD3 with plate- bound antibodies resulted in a marked increase in cell size (consistent with blastogenesis), synergistically increased surface expression of CD25 and CD69, and increased T cell metabolism. Similarly, concomitant ICAM-3 and CD3 stimulation significantly (P < 0.001) increased resting human T cell phosphatidylinositol hydrolysis and phospholipase C-γ1 phosphorylation. These results indicate that ICAM-3 augments signaling through CD3, functioning as a costimulatory molecule for resting T cells in the initial activation step.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Berney SM; Schaan T; Alexander JS; Peterman G; Hoffman PA; Wolf RE; Van Der Heyde H; Atkinson TP
  • Start Page

  • 867
  • End Page

  • 874
  • Volume

  • 65
  • Issue

  • 6