The role of regulatory T cells in the Leishmania (Viannia) panamensis mouse model: a target for immunotherapy. (P3091)

Abstract

Abstract Leishmania (Viannia) parasites are etiological agents of cutaneous leishmaniasis in the New World. Infection in humans is characterized by mixed Th1/Th2 and hyperinflammatory responses. Treg suppressive function is diminished and only restored with disease resolution. Using the mouse model of chronic L. (V.) panamensis infection, we examined the hypothesis that Treg impairment contributes to pathogenesis. Upon infection, Treg CD4+Foxp3+ cell levels were reduced and dysregulated. Treg cells produced IFNγ and had a reduced ability to suppress T cell proliferation in vitro. Ablation of Tregs in DEREG mice resulted in enlarged lesions, increased parasite load and enhanced production of IL-17 and IFNγ. Conversely, adoptive transfer of Tregs from naïve mice halted disease progression, lowered parasite burden and reduced production of IL-10, IL-13, IL-17 and IFNγ. As Treg function appeared to be important for controlling pathogenesis, we examined whether directly modulating Treg function provided a target for immunotherapy. As a proof of principle, chronically infected mice were treated with high dose CpG to induce Tregs. Immediately after treatment, increases in TGFβ and Foxp3+ cells were observed, with an ablation of Foxp3+IFNγ+ cells and reduction of IL-10, IL-13, IL-17 and IFNγ. CpG treatment led to amelioration of disease. Thus, immunotherapy targeting Tregs may provide an alternate treatment strategy for leishmaniasis caused by L. (Viannia) panamensis parasites.