CTLA4 and autoimmune disease: A cell-extrinsic pathway for CTLA-4 was first described by Bachman and coworkers who found that Rag2-deficient mice reconstituted with a mixture of wild-type and CTLA-4-deficient bone marrow cells failed to develop autoimmune disease, while the transfer of Ctla4−/− bone marrow cells alone transferred disease (54).