Indoleamine 2,3-dioxygenase in lung allograft tolerance.

Background: Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in the degradation of tryptophan (Try) to
kynurenine (Kyn), is thought to suppress T-cell activity. Although a few experimental studies have
suggested a role for IDO in graft acceptance, human data are scarce and inconclusive. We sought
to establish whether, in lung transplant recipients (LTRs), plasma IDO activity mirrors the level of
graft acceptance.
Methods: We measured the plasma Kyn/Try ratio, reflecting IDO activity, by high-performance liquid
chromatography (HPLC) in 90 LTRs, including 26 patients who were still functionally/clinically
stable for 36 post-transplant months (stable LTRs) and 64 LTRs with bronchiolitis obliterans
syndrome (BOS, Grades 0-p to 3). Twenty-four normal healthy controls (NHCs) were also included.
Results: The Kyn/Try ratio in stable LTRs resembled that observed in NHCs, whereas, unexpectedly, patients
with BOS, who had lower counts of peripheral CD4 T-regulatory cells and tolerogenic plasmacytoid
dendritic cells than stable LTRs, showed an increased plasma Kyn/Try ratio compared with both NHCs
and stable LTRs. IDO expression by in vitro–stimulated peripheral blood mononuclear cells (PBMC) did
not vary between BOS and stable LTRs. Furthermore, BOS patients displayed signs of chronic systemic
inflammation (increased plasma levels of interleukin-8 and tumor necrosis factor-alpha) and higher T-cell
activation (increased frequency of peripheral interferon-–producing clones).
Conclusions: Our results suggest that, in vivo, in lung transplantation, plasma IDO activity does not reflect the
degree of lung graft acceptance, but instead is correlated with the degree of chronic inflammation.