Low-dose IL-2 falls short of inducing transplant tolerance

While treatment with low-dose interleukin (IL)-2 leads to the expansion of circulating regulatory T cells (Treg), it does not appear to induce allograft tolerance among liver transplant patients, reports a new study.

The trial included six liver transplant recipients who agreed to receive low-dose IL-2 treatment, which was administered 2–6 years after transplantation. Those who showed at least a twofold increase in circulating Treg levels a month after IL-2 treatment were slowly weaned off immunosuppressive treatment over a 4-month period.

In response to treatment, participants demonstrated a progressive increase in circulating Treg levels and reached a more than twofold growth by week 1 in five of six treated patients. All participants reached such a benchmark after 4 weeks.

Five patients were ultimately withdrawn from immunosuppressive tacrolimus treatment, of whom four successfully achieved 75-percent dose reduction. Two patients were able to completely stop tacrolimus medication.

However, all patients experienced allograft dysfunction within 6 months, all cases of which were attributed to T cell-mediated rejection. All patients required reinitiation of immunosuppressive medication. Rejection episodes were mild or moderate in severity and were quickly resolved after restarting tacrolimus.

“Low-dose IL-2 markedly expanded circulating Tregs but did not promote their trafficking into the liver and rendered the allograft more immunogenic as a result of the activation of an interferon gamma-mediated inflammatory response,” the researchers said. “Overall, low-dose IL-2 did not promote, and probably hindered, the development of liver allograft tolerance.”