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Transforming Growth Factor Beta Expression by Human Vascular Cells Inhibits Interferon Gamma Production and Arterial Media Injury by Alloreactive Memory T Cells
Author(s) -
Lebastchi A. H.,
Khan S. F.,
Qin L.,
Li W.,
Zhou J.,
Hibino N.,
Yi T.,
Rao D. A.,
Pober J. S.,
Tellides G.
Publication year - 2011
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2011.03676.x
Subject(s) - medicine , immunology , effector , microbiology and biotechnology , proinflammatory cytokine , transforming growth factor beta , interferon gamma , transforming growth factor , cytokine , biology , inflammation
Arteriosclerosis is characterized by the local activation of effector T cells leading to production of proinflammatory cytokines, such as IFN (interferon)‐γ and IL‐17, within the vessel wall. Conversely, the production of antiinflammatory cytokines, for example, TGF‐β, by regulatory lymphocytes is known to inhibit both the differentiation of naïve 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‐γ, 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‐γ 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 naïve T cells.