Transforming growth factor beta expression by human vascular cells inhibits interferon gamma production and arterial media injury by alloreactive memory T cells

A. H. Lebastchi, S. F. Khan, L. Qin, W. Li, J. Zhou, Narutoshi Hibino, T. Yi, D. A. Rao, J. S. Pober, G. Tellides

Research output: Contribution to journalArticlepeer-review

Abstract

Arteriosclerosis is characterized by the local activation of effector T cells leading to production of proinflammatory cytokines, such as IFN (interferon)-c and IL-17, within the vessel wall. Conversely, the production of antiinflammatory cytokines, for example, TGF-b, by regulatory lymphocytes is known to inhibit both the differentiation of näive T cells into effector T cells and the development of arteriosclerosis in murine models. We investigated the role of TGF-β on the alloreactivity of human effector memory T cells (Tem). Quiescent vascular cells, but not Tem, expressed TGF-β . Blockade of TGF-β activity in cocultures of CD4+ Tem with allogeneic endothelial cells significantly increased IFN-c , but not IL-17, secretion. Additionally, serologic neutralization of TGF-β in immunodeficient mouse hosts of human coronary artery grafts into which allogeneic human T cells were adoptively transferred resulted in heavier medial infiltration by Tem, greater loss of medial smooth muscle cells and increased IFN-c production within the grafts without significantly reducing either intimal injury or IL-17 production. Protective effects of TGF-β may be limited by fewer TGF-β -expressing vascular cells within the intimal compartment, by a reduction in the expression of TGF-β by vascular cells in rejecting grafts, or possibly to less effective suppression of Tem than näive T cells.

Original languageEnglish (US)
Pages (from-to)2332-2341
Number of pages10
JournalAmerican Journal of Transplantation
Volume11
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

Keywords

  • Arteriosclerosis
  • Endothelial cells
  • Interferon-c
  • Smooth muscle cells
  • T cells

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Transforming growth factor beta expression by human vascular cells inhibits interferon gamma production and arterial media injury by alloreactive memory T cells'. Together they form a unique fingerprint.

Cite this