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Am J Pathol. 2002 Oct;161(4):1307-13.

The role of MIG/CXCL9 in cardiac allograft vasculopathy.

Author information

1
Division of Cardiothoracic Surgery, Department of Surgery, University of California at Los Angeles, Los Angeles, California, USA.

Abstract

T lymphocytes play a critical role in chronic rejection of transplanted hearts, or cardiac allograft vasculopathy (CAV). However, the molecular mediators of T lymphocyte recruitment in CAV are incompletely defined. We hypothesized that the chemokine, monokine induced by interferon-gamma (MIG/CXCL9), which induces T lymphocyte migration in vitro, participates in T lymphocyte recruitment in CAV. In a previously characterized MHC II-mismatched murine model of CAV, intragraft MIG/CXCL9 gene transcript and protein levels increased on days 7, 14, and 24 days after transplantation, paralleling T lymphocyte recruitment and preceding intimal thickening. Antibody neutralization of MIG/CXCL9 significantly reduced CD4(+) T lymphocyte infiltration and intimal thickening in this model. MIG/CXCL9 was produced by graft-infiltrating MOMA-2+ macrophages in early and late stages of CAV. And, although T lymphocytes did not produce MIG/CXCL9, recipient CD4(+) T lymphocytes were required for sustained intragraft MIG/CXCL9 production and CAV development. These findings demonstrate that 1) MIG/CXCL9 plays an important role in CD4(+) T lymphocyte recruitment and development of CAV, 2) MOMA-2+ macrophages are the predominant recipient-derived source of MIG/CXCL9, and 3) recipient CD4 lymphocytes are necessary for sustained MIG/CXCL9 production and CAV development in this model. Neutralization of the chemokine MIG/CXCL9 may have therapeutic potential for the treatment of chronic rejection after heart transplantation.

PMID:
12368204
PMCID:
PMC1867280
DOI:
10.1016/S0002-9440(10)64407-0
[Indexed for MEDLINE]
Free PMC Article
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