Imperial College London
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Dr. Beth Holder

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer in Maternal and Fetal Health
 
 
 
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Contact

 

+44 (0)20 7594 1773b.holder Website

 
 
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Location

 

3 008Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Grant:2017:10.1111/cei.12956,
author = {Grant, CR and Holder, BS and Liberal, R and Heneghan, MA and Ma, Y and Mieli-Vergani, G and Vergani, D and Longhi, MS},
doi = {10.1111/cei.12956},
journal = {Clinical and Experimental Immunology},
pages = {71--82},
title = {Immunosuppressive drugs affect interferon (IFN)-γ and programmed cell death 1 (PD-1) kinetics in patients with newly diagnosed autoimmune hepatitis.},
url = {http://dx.doi.org/10.1111/cei.12956},
volume = {189},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Autoimmune hepatitis (AIH) is characterized by overwhelming effector immune responses associated with defective regulatory T cells (Tregs ). Several lines of evidence indicate CD4 as the main effectors involved in autoimmune liver damage. Herein we investigate the in-vitro effects of prednisolone, 6-mercaptopurine, cyclosporin, tacrolimus, mycophenolic acid (MPA) and rapamycin, immunosuppressive drugs (ISDs) used in AIH treatment, on the expression of proinflammatory cytokines, co-inhibitory molecules and ability to proliferate of CD4(+) CD25(-) cells, isolated from the peripheral blood of treatment-naive patients with AIH. We note that in healthy subjects (HS) following polyclonal stimulation and in the absence of ISDs, the expression of interferon (IFN)-γ, interleukin (IL)-17 and tumour necrosis factor (TNF)-α by CD4 effectors peaks at 48 h and decreases at 96 h to reach baseline levels. In contrast, in AIH the expression of all these proinflammatory cytokines continue rising between 48 and 96 h. Levels of programmed cell death-1 (PD-1), T cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) and cytotoxic T lymphocyte antigen-4 (CTLA-4) increase over 96-h culture both in HS and AIH, although with faster kinetics in the latter. Exposure to ISDs contains IFN-γ and PD-1 expression in AIH, where control over CD4(+) CD25(-) cell proliferation is also noted upon exposure to MPA. Treatment with tacrolimus and cyclosporin render CD4(+) CD25(-) cells more susceptible to Treg control. Collectively, our data indicate that in treatment-naive patients with AIH, all ISDs restrain T helper type 1 (Th1) cells and modulate PD-1 expression. Furthermore, they suggest that tacrolimus and cyclosporin may ameliorate effector cell responsiveness to Tregs .
AU  - Grant,CR
AU  - Holder,BS
AU  - Liberal,R
AU  - Heneghan,MA
AU  - Ma,Y
AU  - Mieli-Vergani,G
AU  - Vergani,D
AU  - Longhi,MS
DO  - 10.1111/cei.12956
EP  - 82
PY  - 2017///
SN  - 1365-2249
SP  - 71
TI  - Immunosuppressive drugs affect interferon (IFN)-γ and programmed cell death 1 (PD-1) kinetics in patients with newly diagnosed autoimmune hepatitis.
T2  - Clinical and Experimental Immunology
UR  - http://dx.doi.org/10.1111/cei.12956
UR  - http://www.ncbi.nlm.nih.gov/pubmed/28257599
UR  - http://hdl.handle.net/10044/1/46099
VL  - 189
ER  -
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