The effects of CTLA-4Ig on acute lung allograft rejection: A comparison of intrabronchial gene therapy with systemic administration of protein

Mustafa M. Ugurlu, Matthew D. Griffin, Timothy O'Brien, Henry D. Tazelaar, Virginia M. Miller, Christopher G.A. McGregor

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background. Blockade of T-cell costimulation by local delivery of an adenoviral vector encoding for CTLA-4Ig and systemic administration of the protein are compared in a rat lung allograft model. Methods. Left lungs of Brown Norway rats (RT1n) were transplanted into Lewis (RT11) recipients in four groups of six animals each: 1) no treatment; 2) intrabronchial transduction of donor lung with adenovirus encoding mCTLA-4Ig (adeno-mCTLA-4Ig); 3) intrabronchial transduction with empty adenovirus; and 4) intraperitoneal injection of mCTLA-4Ig. Grading of rejection, mCTLA-4Ig measurement in serum and bronchial washings, RT-PCR for virally encoded transcripts, and immunohistochemistry for mCTLA-4Ig were carried out 4 days later. Results. Intrabronchial transduction with adeno-mCTLA-4Ig resulted in detectable transgene expression in graft tissue and bronchial fluid but not in serum. Significant reduction in rejection grade (from grade 3 to 2) occurred after systemic mCTLA-4Ig but not adeno-mCTLA-4Ig transduction. Conclusion. Local expression of immunomodulatory proteins can be achieved within lung allografts by intrabronchial delivery of adenoviral vector but may not significantly modify acute rejection.

Original languageEnglish (US)
Pages (from-to)1867-1871
Number of pages5
JournalTransplantation
Volume71
Issue number12
DOIs
StatePublished - Jun 27 2001
Externally publishedYes

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