Immune reconstitution autoimmune disease models are generated based on immune-reconstituted mice. Immune-deficient mice are infused with human PBMC (peripheral blood mononuclear cells) or HSC (hematopoietic stem cells) to reconstitute human immune cells, including T cells, B cells, NK cells, myeloid cells, and other immune populations. Specific agents are administered to the mice to induce autoimmune disease phenotypes. These models can be used to evaluate drugs targeting human immune cells.