Lupus-Prone Mice Resist Immune Regulation and Transplant Tolerance Induction.

Stocks BT, Wilhelm AJ, Wilson CS, Marshall AF, Putnam NE, Major AS, Moore DJ
Am J Transplant. 2016 16 (1): 334-41

PMID: 26372909 · PMCID: PMC4718751 · DOI:10.1111/ajt.13449

The strongly immunogenic environment in autoimmune diseases such as lupus may pose a stringent barrier to transplantation. Despite available murine models of lupus, transplant tolerance in this setting has yet to be fully investigated in highly penetrant genetic models of disease. Such studies are of clear clinical importance because lupus is a transplant indication in which transplanted kidneys have a substantially increased risk of rejection including a role for recurrent nephritis. In the fully penetrant B6.SLE123 mouse, we determined that CD4 T follicular helper and germinal center B cells were significantly expanded compared with healthy controls. We traced this expansion to resistance of effector CD4 T and B cells in B6.SLE123 mice to regulation by either CD4 T regulatory cells (CD4Tregs) or CD8 T regulatory cells (CD8Tregs), despite demonstrating normal function by Tregs in this strain. Finally, we determined that B6.SLE123 mice resist anti-CD45RB-mediated tolerance induction to foreign islet allografts, even in the absence of islet autoimmunity. Overall, B6.SLE123 lupus-prone mice are highly resistant to transplant tolerance induction, which provides a new model of failed tolerance in autoimmunity that may elucidate barriers to clinical transplantation in lupus through further cellular and genetic dissection.

© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

MeSH Terms (17)

Animals Autoantibodies Autoimmunity Cells, Cultured Dendritic Cells Graft Rejection Graft Survival Islets of Langerhans Transplantation Lupus Erythematosus, Systemic Lupus Nephritis Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Inbred MRL lpr Mice, Inbred NOD T-Lymphocytes, Regulatory Transplantation Tolerance

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