Allogeneic hematopoietic cell transplantation (HCT) is an effective therapy for treatment of hematological malignancies and various autoimmune conditions. However, HCT traditionally requires conditioning by total body irradiation and/or chemotherapy, both of which are toxic and induce GVHD. Provided herein are compositions and methods for conditioning a subject for HCT by administering one or more anti-CD3 compounds and one or more histone deacetylase inhibitors. Also provided herein are methods for reducing GVHD in a subject receiving total body irradiation prior to HCT comprising administering one or more anti-CD3 compounds to the subject prior to total body irradiation.