Presence of donor-derived thymic epithelial cells in [B6→MRL/lpr] mice after allogeneic intra-bone marrow–bone marrow transplantation (IBM–BMT)

Abstract

We have previously shown that allogeneic intra-bone marrow–bone marrow transplantation (IBM–BMT) can be used to treat autoimmune diseases in MRL/lpr (H-2 K) mice with replacing not only hematolymphoid cells but also stromal cells by normal C57BL/6 (B6: H-2 b) mouse cells. In the present study, we examined for existence of donor-derived thymic epithelial cells (TECs) in the host thymus using green fluorescent protein (GFP)-B6 (H-2 b) mice. In [GFP-B6→MRL/lpr] chimeric mice, splenocytes and thymocytes were completely replaced by donor-type cells, and levels of serum autoantibodies and proteinuria were significantly – reduced to those levels of normal donors. Interestingly, GFP-expressing TECs – not only medullary TECs, which express mouse thymus stromal (MTS)-10, but also cortical TECs, which express cytokeratin 18 – were found. Also, the number of autoimmune regulator (AIRE) expressing TECs, which regulates tissue-specific antigens to delete autoreactive cells, was reduced in the chimeric mice to that of the donor, whereas the number of forkhead box N1 (FOXN1) expressing TECs, which are crucial in the terminal differentiation of TECs, remained unchanged. These findings suggest that BMCs contain the precursors of functional TECs, and that they can differentiate into TECs, thereby correcting thymic function.