T cells in Cardiac Allograft Vasculopathy Are Skewed to Memory Th-1 Cells in the Presence of a Distinct Th-2 Population
Article first published online: 14 APR 2008
DOI: 10.1111/j.1600-6143.2008.02198.x
©2008 The Authors Journal compilation © 2008 The American Society of Transplantation and the American Society of Transplant Surgeons
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How to Cite
Hagemeijer, M. C., Van Oosterhout, M. F. M., Van Wichen, D. F., Van Kuik, J., Siera-de Koning, E., Gmelig Meyling, F. H. J., Schipper, M. E. I., De Jonge, N. and De Weger, R. A. (2008), T cells in Cardiac Allograft Vasculopathy Are Skewed to Memory Th-1 Cells in the Presence of a Distinct Th-2 Population. American Journal of Transplantation, 8: 1040–1050. doi: 10.1111/j.1600-6143.2008.02198.x
Publication History
- Issue published online: 14 APR 2008
- Article first published online: 14 APR 2008
- Received 18 October 2007, revised 10 January 2008 and accepted 30 January 2008
- Abstract
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- References
- Cited By
Keywords:
- Allograft arteriopathy;
- alloreactive T cells;
- chronic allograft rejection;
- coronary artery disease;
- vasculopathy
Neo-intima proliferation in cardiac allograft vasculopathy is induced by a population of T-helper cells that are in majority Th-1 cells producing only few cytokines and are low in CD-markers expression, but directly or indirectly result in high y-interferon and TGF-β production in the arterial wall. See also editorial by Rose in this issue on page 915.
Cardiac allograft vasculopathy (CAV) in heart transplantation (HTx) patients remains the major complication for long-term survival, due to concentric neointima hyperplasia induced by infiltrating mononuclear cells (MNC). Previously, we showed that activated memory T-helper-1 (Th-1) cells are the major component of infiltrating MNC in coronary arteries with CAV. In this study, a more detailed characterization of the MNC in human coronary arteries with CAV (n = 5) was performed and compared to coronary arteries without CAV (n = 5), by investigating MNC markers (CD1a, DRC-1, CD3, CD20, CD27, CD28, CD56, CD68, CD69, FOXP3 and HLA-DR), cytokines (IL-1A, 2, 4, 10, 12B, IFN-γ, and TGF-β1), and chemokine receptors (CCR3, CCR4, CCR5, CCR7, CCR8, CXCR3 and CX3CR1) by immunohistochemical double-labeling and quantitative PCR on mRNA isolated from laser microdissected layers of coronary arteries. T cells in the neointima and adventitia of CAV were skewed toward an activated memory Th-1 phenotype, but in the presence of a distinct Th-2 population. FOXP3 positive T cells were not detected and production of most cytokines was low or absent, except for IFN-γ, and TGF-β. This typical composition of T-helper cells and especially production of IFN-γ and TGF-β may play an important role in the proliferative CAV reaction.

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