Memory T cells and their costimulators in human allograft injury

J Immunol. 2005 Oct 15;175(8):4886-96. doi: 10.4049/jimmunol.175.8.4886.

Abstract

Both CD4(+) and CD8(+) human memory but not naive T cells respond to allogeneic human dermal microvascular endothelial cells (HDMEC) in vitro by secreting cytokines and by proliferating. Several recently identified costimulators, namely, 4-1BB ligand, ICOS ligand, and OX40 ligand, are up-regulated on cultured HDMEC in response to TNF or coculture with allogeneic T cells. Blockade of these costimulators each partially reduces IFN-gamma and IL-2 secretion and proliferation of previously resting memory T cells. The effects of these costimulators are overlapping but not identical. Memory but not naive T cells are the principal effectors of microvascular injury in human skin allografts following adoptive transfer into immunodeficient mice. Furthermore, blocking 4-1BB ligand, ICOS ligand, or OX40 ligand in this model reduces human skin allograft injury and T cell effector molecule expression. These data demonstrate that human memory T cells respond to microvascular endothelial cells and can injure allografts in vivo without priming. Furthermore, several recently described costimulators contribute to these processes.

Publication types

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

MeSH terms

  • 4-1BB Ligand
  • Animals
  • Antigens, CD
  • Cells, Cultured
  • Coculture Techniques
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • Humans
  • Immunologic Memory / immunology*
  • Inducible T-Cell Co-Stimulator Ligand
  • Lymphocyte Activation / immunology*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, SCID
  • OX40 Ligand
  • Proteins / genetics
  • Proteins / metabolism
  • Skin Transplantation / immunology
  • T-Lymphocytes / immunology*
  • Transplantation, Homologous / pathology*
  • Tumor Necrosis Factors / biosynthesis
  • Tumor Necrosis Factors / genetics

Substances

  • 4-1BB Ligand
  • Antigens, CD
  • ICOSLG protein, human
  • Inducible T-Cell Co-Stimulator Ligand
  • Membrane Glycoproteins
  • OX40 Ligand
  • Proteins
  • TNFSF4 protein, human
  • TNFSF9 protein, human
  • Tnfsf9 protein, mouse
  • Tumor Necrosis Factors