Repeated long-term DT application in the DEREG mouse induces a neutralizing anti-DT antibody response

Regulatory t (tregs) cells play an important role in mediating tolerance to self-antigens but can also mediate detrimental tolerance to tumours and pathogens in a foxp3-dependent manner. genetic tools exploiting the foxp3 locus including bacterial artificial chromosome-(bac-) transgenic depletion of regulatory t cells (dereg) mice have provided essential information on treg biology and the potential therapeutic modulation of tolerance. in dereg mice,foxp3+ tregs selectively express enhanced green fluorescent protein (egfp) and diphtheria toxin (dt) receptor,allowing for the specific depletion of tregs through dt administration. we here provide a detailed overview about an important consideration that long-term administration of dt induces a humoral immune response with an appropriate production of anti-dt antibodies that can inactivate dt and thus abrogate its effect in the dereg mouse. additionally,we showed that anti-dt mouse serum partially neutralized dt-induced foxp3 inhibition. © 2016 junhua wang et al.