Aetiopathogenesis
Anti-fibrotic characteristics of Vγ9+ γδ T cells in systemic sclerosis
N. Markovits1, A. Bendersky2, R. Loebstein3, M. Brusel4, E. Kessler5, I. Bank6
- Department of Medicine A, Chaim Sheba Medical Center, Tel Hashomer; and Institute of Clinical Pharmacology, Sheba Medical Center, Tel Hashomer, Israel. noamarkovits@gmail.com
- Laboratory for Immunoregulation, Chaim Sheba Medical Center, Tel Hashomer; and Sackler School of Medicine, Tel Aviv University, Israel.
- Institute of Clinical Pharmacology, Sheba Medical Center, Tel Hashomer; and Sackler School of Medicine, Tel Aviv University, Israel.
- Sackler School of Medicine, Tel Aviv University; and Maurice & Gabriela Goldschleger Eye Research Institute, Sheba Medical Center, Tel Hashomer, Israel.
- Sackler School of Medicine, Tel Aviv University; and Maurice & Gabriela Goldschleger Eye Research Institute, Sheba Medical Center, Tel Hashomer, Israel.
- Laboratory for Immunoregulation, Chaim Sheba Medical Center, Tel Hashomer; Department of Medicine F, Chaim Sheba Medical Center, Tel Hashomer; and Sackler School of Medicine, Tel Aviv University, Israel. ibank@post.tau.ac.il
CER8799
2016 Vol.34, N°5 ,Suppl.100
PI 0023, PF 0029
Aetiopathogenesis
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PMID: 26886502 [PubMed]
Received: 22/07/2015
Accepted : 23/11/2015
In Press: 09/02/2016
Published: 13/10/2016
Abstract
OBJECTIVES:
γδ T cells of the Vγ9Vδ2 subtype secrete anti-fibrotic cytokines upon isopentenyl pyrophosphate (IPP) stimulation. In this study, we sought to compare IPP and Zoledronate, an up-regulator of IPP, effects on proliferation and cytokine secretion of Vγ9+ T cells from systemic sclerosis (SSc) patients and healthy controls (HCs). We also examined the effect of IPP-triggered peripheral blood mononuclear cells (PBMC) on fibroblast procolla- gen secretion.
METHODS:
PBMC from SSc patients and HCs were stimulated by increasing concentrations of Zoledronate, with or without IPP, and Vγ9+ T cell percentages were calculated using FACScan analysis. Subsequently, PBMC were cultured with IPP or toxic shock syndrome toxin-1 (TSST-1), and contents of the anti-fibrotic cytokines tumour necrosis factor (TNF)-α and interferon (IFN)-γ were measured by ELISA kits. Finally, supernatants of IPP-triggered Vγ9+ T cells from SSc patients were added to fibroblast cultures, and relative intensities of procollagen α1 chains were determined by densinometry.
RESULTS:
Higher concentrations of Zoledronate were required for maximal proliferation of Vγ9+ T cells in 9 SSc patients compared to 9 HCs, irrespective of exogenous IPP. When compared to stimulation by TSST-1, a non-Vγ9+ selective reagent, secretion of the anti-fibrotic cytokines TNF-α and IFN-γ in response to IPP was relatively diminished in SSc but not in HCs. Reduction of procollagen secretion by fibroblasts cultured with supernatants of IPP-stimulated PBMC was observed only in some SSc patients.
CONCLUSIONS:
Activated Vγ9+ T cells could act as anti-fibrotic mediators in SSc, although decreased responsiveness to IPP may play a role in the pathological fibrosis of this disease.
