An anti-CD103 immunotoxin promotes long-term survival of pancreatic islet allografts

Am J Transplant. 2009 Sep;9(9):2012-23. doi: 10.1111/j.1600-6143.2009.02735.x. Epub 2009 Jul 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antigens, CD / chemistry*
  • CD8-Positive T-Lymphocytes / cytology
  • Female
  • Immunosuppression Therapy
  • Integrin alpha Chains / chemistry*
  • Integrins / metabolism
  • Islets of Langerhans / cytology*
  • Islets of Langerhans Transplantation / methods*
  • Leukocytes / cytology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Thymus Gland / cytology
  • Transplantation, Homologous


  • Antibodies, Monoclonal
  • Antigens, CD
  • Integrin alpha Chains
  • Integrins
  • alpha E integrins