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

Abstract

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.

Immunoregulatory Effects of Myeloid-Derived Suppressor Cell Exosomes in Mouse Model of Autoimmune Alopecia Areata

“…Instead, reduced GZMB, GZMC, PRF1 ( 115 ), FasL ( 116 ), Rab27a ( 117 ), and TNFSF10 (TRAIL) ( 118 ) expression can account for mitigated CTL activity. Impaired IFNγ secretion, IL2R and IL12R expression may hamper overshooting reactivity of the adaptive immune system ( 119 ). B cell activation could become impeded by reduced adhesion G protein coupled receptor G3 (Adgrg3) ( 120 ), CKLF like MARVEL transmembrane domain containing 7 (CMTM7) ( 121 ), and Myb expression ( 122 ).…”

The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration

“…Both complications are related to T-cell function [ 9 , 10 ]. High T-cell activity after transplantation can cause increased rejection, whereas diminished T-cell function can increase the risk of CMV infection [ 11 , 12 ]. Despite immunomodulatory therapy, it is difficult to maintain an immune reaction balance between effective avoidance of CMV infection and immune tolerance to the graft [ 12 ].…”

Variations in DNA methylation of interferon gamma and programmed death 1 in allograft rejection after kidney transplantation

“…An important player of the host immune response is the pro-inflammatory cytokine IFNγ, and high expression of IFNγ is associated with both acute and chronic allograft rejection [9–11]. The expression of IFNγ is regulated by DNA methylation with the addition of methyl groups on cytosine-phosphate-guanine sites (CpGs) in the IFNγ promoter region silencing its expression.…”