IFN-γ: The Dr. Jekyll and Mr. Hyde of Immunology?

Evaristo, César; Alegre, Maria‐Luisa

doi:10.1111/ajt.12468

Cited by 5 publications

(3 citation statements)

References 5 publications

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“…Although IFN-g is commonly associated with immunostimulatory and proinflammatory effects, its activity is pleiotropic and it also has anti-inflammatory activity. 28,29 Paradoxically, in some physiological circumstances, IFN-g elicits inflammatory Th1-driven immune responses, whereas in others, it enables Treg cells to control immune responses. The early and rapid production of IFN-g by induced Treg cells has been shown to be important for the functional activity of both the Treg cells themselves and for that of other T cells in the same physiological environment.…”

Section: Interferon-gmentioning

confidence: 99%

“…It has also been postulated that there may be a threshold in the number of antigen-specific T-cell precursors beyond which IFN-g mediates immunostimulation instead of immunomodulation. 29,31 Thus, in contrast to the proinflammatory effects of relatively high concentrations of IFN-g, low-dose concentrations are likely to exert suppressive effects on T-cell activation and trafficking.…”

Section: Interferon-gmentioning

confidence: 99%

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T-Cell Cytokines as Predictive Markers of the Risk of Allograft Rejection

Brunet

López

López-Hoyos

2016

Therapeutic Drug Monitoring

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Over the last decade, several biomarkers and surrogate markers have surfaced as promising predictive markers of risk of rejection in solid organ transplantation. The monitoring of these markers can help to improve graft and recipient care by personalizing immunomodulatory therapies. The complex immune system response against an implanted graft can change during long-term follow-up, and the dynamic balance between effector and regulatory T-cell populations is a crucial factor in antidonor response, risk of rejection, and immunosuppression requirements. Therefore, at any time before and after transplantation, T-effector activity, which is associated with increased production and release of proinflammatory cytokines, can be a surrogate marker of the risk of rejection and need for immunosuppression. In addition, immunosuppressive drugs may have a different effect in each individual patient. The pharmacokinetics and pharmacodynamics of these drugs show high interpatient variability, and pharmacodynamic markers, strongly associated with the specific mechanism of action, can potentially be used to measure individual susceptibility to a specific immunosuppressive agent. The monitoring of a panel of valid biomarkers can improve patient stratification and the selection of immunosuppressive drugs. After transplantation, therapy can be adjusted based on the prediction of rejection episodes (maintained alloreactivity), the prognosis of allograft damage, and the individual's response to the drugs. This review will focus on current data indicating that changes in the T-cell production of the intracellular cytokines interferon-γ and interleukin-2 could be used to predict the risk of rejection and to guide immunosuppressive therapy in transplant recipients.

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Section: Interferon-gmentioning

confidence: 99%

Section: Interferon-gmentioning

confidence: 99%

T-Cell Cytokines as Predictive Markers of the Risk of Allograft Rejection

Brunet

López

López-Hoyos

2016

Therapeutic Drug Monitoring

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“…The effect of IFN-g in corneal allografts is still not well established [49,50]. Nicholls and Dick [51] reported that IFN-g synthesis is absent in the anterior chamber during the rejection process.…”

Section: Ifn-g Is Crucial For Induction Of Gr-1 Int Cd11b + Mdscs In mentioning

confidence: 99%

Gr-1intCD11b+ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival

Choi

Ham

et al. 2016

Journal of Leukocyte Biology

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We identified the characteristics of myeloid-derived suppressor cells (MDSCs) and investigated their mechanism of induction and their functional role in allograft rejection using a murine corneal allograft model. In mice, MDSCs coexpress CD11b and myeloid differentiation antigen Gr-1. Gr-1CD11b cells infiltrated allografted corneas between 4 d and 4 wk after surgery; however, the frequencies of Gr-1CD11b cells were not different between accepted and rejected allografts or in peripheral blood or BM. Of interest, Gr-1CD11b cells, but not Gr-1CD11b cells, infiltrated the accepted graft early after surgery and expressed high levels of immunosuppressive cytokines, including IL-10, TGF-β, and TNF-related apoptosis-inducing ligand. This population remained until 4 wk after surgery. In vitro, only high dose (>100 ng/ml) of IFN-γ plus GM-CSF could induce immunosuppressive cytokine expression in Gr-1CD11b cells. Furthermore, adoptive transfer of Gr-1CD11b cells reduced T cell infiltration, which improved graft survival. In conclusion, high-dose IFN-γ in allograft areas is essential for development of Gr-1CD11b MDSCs in corneal allografts, and subtle environmental changes in the early period of the allograft can result in a large difference in graft survival.

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Cytokine-based immune monitoring

Millán

Brunet

2016

Clinical Biochemistry

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IFN-γ: The Dr. Jekyll and Mr. Hyde of Immunology?

Cited by 5 publications

References 5 publications

T-Cell Cytokines as Predictive Markers of the Risk of Allograft Rejection

T-Cell Cytokines as Predictive Markers of the Risk of Allograft Rejection

Gr-1intCD11b+ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival

Cytokine-based immune monitoring

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