It is possible that disrupting early IDO-Treg cross-talk that would lead to TCD8 activation requires robust participation by a high number of cognate TCD8 such as adoptively transferred OT-I or vaccine-primed TCD8 examined in the above studies by Sharma et al. This may not necessarily mirror the involvement of Ag-specific TCD8 present in low numbers in a pre-immune repertoire such as site IV-specific TCD8 in IDO−/− mice prior to the inoculation of these animals with T Ag+ tumor cells. Here, IDO1 is linked to neoplasm.