IL-10 transgenic mice present a defect in T cell development reminiscent to SCID patients

To analyze the effect of IL-10 overexpressed by APCs as observed in some SC ID patients, we have expressed the human IL-IO cDNA under the control of th e murine MHC class II promoter in transgenic mice. Similar to SCID patients , these mice presented a defect in T cell maturation characterized by a rap id thymic aplasia that started after birth. The blockage In T cell maturati on was strictly restricted to TCR-alpha beta T cells as the absolute number of thymic dendritic, TCR-gamma delta and NK1.1 T cells were equivalent to control littermates. Crossing IL-10 transgenic mice with TCR transgenic mic e or treatment with staphylococcal enterotoxin B showed that the defect was not related to the impairment of positive or negative selection. However, repopulating of IL-10 transgenic mouse-fetal thymic organ culture with diff erent stages of triple negative T cells isolated from control mice showed t hat the blockage occurred specifically at the pre-T cell stage and was reve rted by treatment with blocking anti-IL-10 mAbs, These results demonstrate that IL-10 regulates T cell maturation and that dysregulation of IL-10 expr ession can lead to severe T cell immunodeficiency.