Intrahepatic Detection of FOXP3 Gene Expression After Liver Transplantation Using Minimally Invasive Aspiration Biopsy

Abstract

Intragraft accumulation of Forkhead box P3 (FOXP3)-positive regulatory T cells (Treg) is associated with local suppression of alloresponses in transplantation models. In the current study, the utility of the minimally invasive fine needle aspiration biopsy for the intragraft detection of FOXP3 and interferon (IFN)-gamma mRNA expression was investigated in clinical liver transplantation (LTx). Intragraft FOXP3 increased within the first year after LTx, but not in blood. Elevated FOXP3, but not IFN-gamma expression, in the liver was observed after hepatitis C virus (HCV) reinfection and after a previous episode of acute rejection. These data show the feasibility of aspiration biopsy for intragraft monitoring of gene expression. Intrahepatic FOXP3 levels are associated with HCV reinfection, a history of acute rejection, and increased within the first year after LTx. Differences in gene expression between the graft and blood underline the importance of local immune monitoring.

Characterization of HCV-Specific CD4+Th17 Immunity in Recurrent Hepatitis C–Induced Liver Allograft Fibrosis

“…Patients with severe fibrosis (Groups 2 and 3) had higher number of Tregs compared to Group 1. These results support previous findings demonstrating increased expression of Foxp3 in the allograft following OLT in recurrent HCV (34). Furthermore, addition of Tregs to HCV specific CD4+ T cells derived from OLTr significantly dampened IFN-γ but not IL-17 secretion (Figure 3B).…”

The Human “Treg MLR”: Immune Monitoring for FOXP3+ T Regulatory Cell Generation

“…Controversy exists, however, regarding the role of FOXP3 + expression in humans, also found in CD25 - cells and CD8 + T cells (10, 11) and during activation in vitro (3). Moreover, organ transplant recipients have demonstrated FOXP3 + cells in high percentages in the peripheral blood, urine and allograft in rejection as well as in operational tolerance (12-17). Therefore, the diagnostic utility of Treg and FOXP3 detection in humans requires understanding these mechanisms more definitively.…”

Human FOXP3+ Regulatory T Cells in Transplantation

“…These data also show the differences in gene expression between the graft and blood seen for multiple organ types, underlining the importance of local immune monitoring (23). Furthermore, to establish a reliable correlation between FOXP3 expression and graft acceptance, other confounding factors need to be considered (e.g., immunosuppressive therapy).…”