Herein, we demonstrated that Vβ11+/Vα5+ DN T cells derived from TCR × HBeAg dbl-Tg mice represent a unique population that possesses a distinctive cell surface marker phenotype, (i.e. TCR+, Thy-1.2+, CD4−, CD8−, CD25low, GITR+, PD-1+, FoxP3−). Furthermore, our data directly show that this DN T-cell population possesses suppressive function against effector T cells specific for the same HBeAg specificity as well as non-specific T cells. In contrast to cTreg cells, the Vβ11+ DN T cells defined

in this model system possess a vigorous proliferative capacity upon in vitro antigenic stimulation and represent as much as 70% (it varies between 50 and 70%) of the cells remaining after 4 days of in vitro culture. Those characteristics are unique and a similar Treg cell population has not been previously reported. RXDX-106 concentration We therefore refer Fostamatinib clinical trial to this unique population as DN Treg cells. Considering that this DN Treg cell population is only observed in TCR-Tg mice, which also express the secreted HBeAg and their strong suppressive effect, HBeAg-specific DN Treg cells may play

a role in tolerance induction by HBeAg in the murine model system. We do not know if an identical DN Treg cell population may exist in chronically infected humans; however, in the mouse model the HBeAg, but not the HBcAg, has the potential to elicit Treg cells in vivo. Therefore, the induction of HBeAg-specific Treg cells may be added to the repertoire of mechanisms by which the secreted HBeAg mediates T-cell tolerance. Recent publications have suggested that Treg cells may contribute to impaired immune function in an HBV-Tg mouse model 44 and in chronic HBV patients.45–47 Furthermore, in one

study, in which the T-cell response to HBcAg was studied, an increase in Treg cell frequency and function was observed in HBeAg-positive compared with HBeAg-negative patients, suggesting a role for HBeAg.46 The previous studies of Treg cells in either an HBV-Tg mouse model or HBV patients have concentrated exclusively on CD25+ Treg cells or cTreg cells. The HBeAg-specific DN Treg cells observed in the 7/16-5 × HBeAg dbl-Tg mouse model may serve as Racecadotril a useful tool to study the functional characteristics of HBeAg-specific Treg cells in general such as clonal expansion and mechanisms of suppression, which may have implications for viral persistence during natural HBV infection. However, to relate the presence and function of DN Treg cells to T-cell tolerance and chronicity in HBV infection will require further studies. In contrast to anergic cTreg cells that lack efficient in vitro expansion, HBeAg-specific DN Treg cells proliferate vigorously in vitro, suggesting that this DN Treg cell population may be a useful tool to elucidate the proliferative potential of Treg cells in general.