The present disclosure is directed to systems, compositions and methods for promoting immune tolerance to an antigen in a subject. Systems and methods provide for introducing directly into at least one lymph node(s) of the subject a therapeutically effective amount of a composition comprising an antigen associated with an autoimmune disease or disorder, in combination with a carrier comprising an immune modulatory agent such that an immune response to said antigen is inhibited or suppressed in the subject. The present disclosure is also directed to systems, compositions and methods for the treatment and/or prevention of autoimmune diseases and conditions, and in particular type 1 diabetes and graft rejection.