Kinetics of costimulatory molecule expression by T cells and dendritic cells during the induction of tolerance versus immunity in vivo.
Steady-state dendritic cells (DC) present peptide-MHC complexes to T cells in a tolerogenic manner, presumably because of deficient costimulation. However, it is clear that the path to tolerance involves initial T cell activation, suggesting that the deficit may lie in late-acting costimulatory molecules. With this in mind we have investigated the kinetics of expression of several costimulatory pairs on DC and OVA-reactive T cells after i.v. injection of mice with peptide and LPS (immunity), or peptide alone (tolerance). We find that T cells up-regulate CD154, OX40, RANKL and PD-1 whether they are destined for tolerance or immunity, although there are some differences in the levels and length of expression. In contrast, when analyzing DC, we found that up-regulation of CD80, CD86, CD40, RANK and PDL-1 occurred only when peptide was co-administered with LPS. These data give a picture of the T cell looking for costimulatory cues that are not forthcoming when pMHC is presented by steady-state DC, leading to tolerance. However, we did see a strong and rapid up-regulation of RANKL on T cells that occurred specifically when peptide was given in the absence of LPS, suggesting a possible positive signal influencing the decision between tolerance and immunity.
Hochweller
Kristin
K
Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK.
Anderton
Stephen M
SM
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D007107:Immune System / Q000276:immunology / Q000502:physiology*; D007108:Immune Tolerance / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D002352:Carrier Proteins; C497965:Cd86 protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D023201:CD40 Ligand