Kinetics of costimulatory molecule expression by T cells and dendritic cells during the induction of tolerance versus immunity in vivo

Abstract

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.