Treg cell depletion in adult mice results in activation of antigen-presenting cells prior to fatal autoimmune disease

Abstract Studies in mice expressing the diphtheria toxin receptor (DTR) exclusively on regulatory T (Treg) cells (Foxp3-DTR mice) demonstrated critical importance of Treg maintaining normal immune homeostasis. Adult Foxp3-DTR injected with DT begin to die from day 10 after treatment. Marked expansion almost all cell types was observed prior death. The purpose present studies examine in-depth changes lymphocytes and antigen-presenting at early time points depletion determine most controlled by steady state. Complete 2 days treatment, but profound activation CD4 +and CD8 +T as measured induction CD44 expression vigorous proliferation Ki-67 incorporation were not seen 6 Curiously, hiKi-67 CD25 −and plasma levels intracellular IL-2 increased suggesting that result a burst production. Increased CD80, CD86, CD40, PD-L1 could be detected CD11c +dendritic (DCs) 6. Anti-CD80/CD86 mAbs reversed provoked cells, while anti-IL-2 or anti-IL-2Rb had no effect. Taken together, these suggest disruption regulation Treg-mediated control DC represents first step complex autoimmune disease depletion. This work supported Intramural Research Program NIAID, NIH.