We show that the i35-Bregs suppress alloreactive responses by inducing alloreactive T cells to upregulate checkpoint proteins (PD-1, LAG-3) associated with T-cell exhaustion/anergy, suggesting that efficacy of i35-Breg immunotherapy may derive in part from reduced capacity of the alloreactive T cells to induce cytotoxicity or produce cytokine storms that exacerbate GVHD. The gene discussed is PDCD1; the disease is graft versus host disease.