An Anti-CD103 Immunotoxin Promotes Long-Term Survival of Pancreatic Islet Allografts

作者：Zhang L; Moffatt Bruce S D; Gaughan A A; Wang J J; Rajab A; Hadley G A^*

来源：American Journal of Transplantation, 2009, 9(9): 2012-2023.

DOI：10.1111/j.1600-6143.2009.02735.x

• CD8 T lymphocytes
• immunosuppression
• integrin
• pancreatic islet transplantation
• regulatory T cells
• thymus

Previous studies using knockout mice document a key role for the integrin CD103 in promoting organ allograft rejection and graft-versus-host disease. However, a determination of whether blockade of the CD103 pathway represents a viable therapeutic strategy for intervention in these processes has proven problematic due to the lack of reagents that efficiently deplete CD103( ) cells from wild type hosts. To circumvent this problem, we conjugated the nondepleting anti-CD103 monoclonal antibody, M290, to the toxin, saporin, to produce an immunotoxin (M290-SAP) that efficiently depletes CD103( ) cells in vivo. Herein, we show that M290-SAP dramatically reduces the frequency and absolute numbers of CD103-expressing leukocytes in the blood, spleen, mesenteric lymph nodes and intestinal epithelium of treated mice. We further demonstrate that M290-SAP promotes indefinite islet allograft survival in a fully MHC mismatched mouse model. The prolonged islet allograft survival resulting from M290-SAP treatment was associated with multiple effects in the host immune system including not only depletion of CD103-expressing leukocytes, but also an increase in CD4( )CD25( )FoxP3( ) T regulatory cells and a predominance of effector-memory CD8 T cells. Regardless of the underlying mechanisms, these data document that depletion of CD103-expressing cells represents a viable strategy for therapeutic intervention in allograft rejection.

• 出版日期2009-9
• 单位哈尔滨医科大学