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TGF‐β Inhibition of CTL Re‐Stimulation Requires Accessory Cells and Induces Peroxisome‐Proliferator‐Activated Receptor‐Gamma (PPAR‐γ)
Author(s) -
VanBuskirk A. M.,
Lesinski G. B.,
Nye K. J.,
Carson W. E.,
Yee L. D.
Publication year - 2006
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.1600-6143.2006.01387.x
Subject(s) - peroxisome proliferator activated receptor , stimulation , medicine , peroxisome proliferator activated receptor gamma , peroxisome proliferator , receptor , peroxisome proliferator activated receptor alpha , microbiology and biotechnology , cancer research , ctl* , peroxisome , nuclear receptor , transcription factor , immunology , biochemistry , biology , immune system , gene , cd8
Effective cellular immunity to Epstein‐Barr virus (EBV), necessary to prevent or cure many post‐transplant lymphoproliferative disorders (PTLD), can be inhibited by transforming growth factor‐beta (TGF‐β). In vitro , TGF‐β inhibits memory CTL re‐stimulation from whole PBMC. We show that the effect of TGF‐β on CTL re‐stimulation is not directly on the T cell, but requires an accessory cell (AC) population. Further, pre‐treatment of AC with TGF‐β significantly reduces memory CTL re‐stimulation and suppresses delayed type hypersensitivity (DTH) responses. Addition of exogenous interferon‐gamma to the AC overcomes the effects of TGF‐β. TGF‐β pre‐treatment also up‐regulates expression of peroxisome‐proliferator‐activated receptor‐gamma (PPAR‐γ) in CD14 + AC. Importantly, pre‐treatment of AC with the PPAR‐γ ligand, ciglitazone, results in significantly reduced memory CTL re‐stimulation. Thus, the effects of TGF‐β in this system may be mediated in part via PPAR‐γ, and PPAR‐γ activation could have significant inhibitory effects on memory T‐cell responses by affecting AC function. These data have important implications in understanding how memory CTL are re‐stimulated and function to prevent disease, especially PTLD.

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