Compositions and methods are provided for generating T cells having a regulatory phenotype from conventional T (Tconv) cells. Such compositions and methods include culturing isolated, naïve Tconv cells with an effective amount of interleukin-35 (IL-35) until the cells have the regulatory phenotype. Also provided are methods to treat subject having or susceptible to having various disorders including, for example, immune system disorders with the T cells having the regulatory phenotype.