The invention is directed to a method of determining whether an agent causes immune toxicity in a human comprising administering the agent to a non-human mammal that has been engrafted with human hematopoietic stem cells (HSCs) and administered one or more human cytokines and determining whether the agent causes immune toxicity in the non-human mammal. If the agent causes immune toxicity in the non-human mammal then the agent causes toxicity in a human. The invention is also directed to a method of determining whether administration of an agent causes cytokine release syndrome in an individual in need thereof comprising administering the agent to a non-human mammal that has been engrafted with HSCs and administered one or more human cytokines and determining whether the agent causes cytokine release syndrome in the non-human mammal. If the agent causes cytokine release syndrome in the non-human mammal then the agent will cause cytokine release syndrome in the human.
