Memory T cells and their costimulators in human allograft injury.
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.
Shiao
Stephen L
SL
Section of Immunobiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
McNiff
Jennifer M
JM
Pober
Jordan S
JS
D053330:4-1BB Ligand; D000818:Animals; D015703:Antigens, CD; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D060945:Inducible T-Cell Co-Stimulator Ligand; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D053278:OX40 Ligand; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000473:pathology*; D048069:Tumor Necrosis Factors / Q000096:biosynthesis / Q000235:genetics
D053330:4-1BB Ligand; D015703:Antigens, CD; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D011506:Proteins; C089251:TNFSF4 protein, human; C505974:TNFSF9 protein, human; C505975:Tnfsf9 protein, mouse; D048069:Tumor Necrosis Factors