Isolated anti-human CD45RC antibodies or binding fragments thereof, nucleic acids and expression vector encoding the same, compositions including the same, and uses thereof as medicaments, including for the prevention and/or treatment of CD45RChigh-related diseases (including autoimmune diseases, undesired immune responses, monogenic diseases, and lymphoma or cancer), in particular for use in preventing and/or treating graft-versus-host disease (GVHD).