Role of ICOS pathway in autoimmune and alloimmune responses in NOD mice

Mohammed Javeed I Ansari, Paolo Fiorina, Shirine Dada, Indira Guleria, Takuya Ueno, Xueli Yuan, Subbulaxmi Trikudanathan, R. Neal Smith, Gordon Freeman, Mohamed H. Sayegh*

*Corresponding author for this work

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Islet allografts are subject to alloimmune and autoimmune destruction when transplanted into autoimmune prone animals or humans. The ICOS-B7h pathway plays a role in alloimmune responses, but its function in autoimmunity against islet cells is controversial. We investigated the role of ICOS signaling in autoimmune and alloimmune responses in NOD mice. ICOS blockade prevents development of spontaneous disease in pre-diabetic NOD mice. Furthermore, while ICOS blockade prolongs graft survival in a fully mismatched non-autoimmune islet allograft model in C57BL/6 recipients, it has no beneficial effect in reversing diabetes in models of islet transplantation in NOD mice involving autoimmunity alone or both allo- and autoimmunity. Interestingly, ICOS blockade is effective in prolonging heart allograft (not subject to tissue-specific autoimmunity) survival in NOD mice. We conclude that in islet transplantation and autoimmune diabetes, ICOS blockade can be effective in inhibiting alloimmunity and preventing autoimmunity but is ineffective in inhibiting recurrence of autoimmunity.

Original languageEnglish (US)
Pages (from-to)140-147
Number of pages8
JournalClinical Immunology
Volume126
Issue number2
DOIs
Publication statusPublished - Feb 1 2008

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Keywords

  • Autoimmune diabetes
  • Costimulation
  • ICOS
  • Islet transplantation
  • NOD mice
  • Sirolimus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Ansari, M. J. I., Fiorina, P., Dada, S., Guleria, I., Ueno, T., Yuan, X., ... Sayegh, M. H. (2008). Role of ICOS pathway in autoimmune and alloimmune responses in NOD mice. Clinical Immunology, 126(2), 140-147. https://doi.org/10.1016/j.clim.2007.07.019