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An Anti‐CD103 Immunotoxin Promotes Long‐Term Survival of Pancreatic Islet Allografts
Author(s) -
Zhang L.,
MoffattBruce S. D.,
Gaughan A. A.,
Wang JJ.,
Rajab A.,
Hadley G. A.
Publication year - 2009
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2009.02735.x
Subject(s) - immunotoxin , alloimmunity , medicine , mesenteric lymph nodes , foxp3 , islet , immunology , cancer research , transplantation , il 2 receptor , knockout mouse , monoclonal antibody , antigen , immune system , antibody , t cell , receptor , endocrinology , diabetes mellitus
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.