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Preventing effect of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies on murine islet allograft rejection

Authors
  • Arai, Kosuke1
  • Sunamura, Makoto1
  • Wada, Yasushi1
  • Takahashi, Motoyoshi2
  • Kobari, Masao1
  • Kato, Kazunori3
  • Yagita, Hideo3
  • Okumura, Ko3
  • Matsuno, Seiki1
  • 1 Tohoku University School of Medicine, First Department of Surgery, 1-1 Seiryo-cho, Aoba-ku, Sendai, 980-8574, Japan , Sendai
  • 2 Tohoku University School of Dentistry, Second Department of Oral Surgery, Sendai, Japan , Sendai
  • 3 Juntendo University School of Medicine, Department of Immunology, Tokyo, Japan , Tokyo
Type
Published Article
Journal
International Journal of Pancreatology
Publisher
Humana Press
Publication Date
Aug 01, 1999
Volume
26
Issue
1
Pages
23–31
Identifiers
DOI: 10.1385/IJGC:26:1:23
Source
Springer Nature
Keywords
License
Yellow

Abstract

Immunosuppressive potentials of the blockade of intercellular adhesion molecule-1 (ICAM)-1/leukocyte function-associated antigen 1 (LFA-1) were examined in a murine islet allotransplantation model by using blocking monoclonal antibodies (MAbs) against these molecules. Isolated islets from ICR mice were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice. Antibodies were administered immediately after transplantation at a dose of 100 µg/mouse/d for 3 or 7 d. In non-treated mice, islet grafts were rejected within 16 d, but the treatment with an anti-ICAM-1 MAb (KAT-1) alone, with anti-LFA-1 MAb (KBA) alone, or with both MAbs significantly prolonged the graft survival. In particular, the combination of KAT-1 and KBA in a 7-d course produced a marked prolongation and induced indefinite graft survivals over 100 d in 88% of recipients. Expression of cytokine transcripts within the islet allografts was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). In the mice treated with KAT-1 and KBA, the transcripts for Th1 cytokines (interleukin 2 [IL-2] and interferon gamma [IFN-γ]) were not detected, but the expression of Th2 cytokines (IL-4 and IL-10) was enhanced and persisted over 140 d. In contrast, Th1 cytokines were dominantly expressed in the grafts from untreated mice. These results indicate that administration of anti-ICAM-1 and/or anti-LFA-1 MAbs prolongs murine islet allograft survival potentially by indicating a Th2 deviation.

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