Comprehensive phenotyping of regulatory T cells after liver transplantation

Abstract

Regulatory T cells (Tregs) play an important role in controlling alloreactivity after solid organ transplantation, but they may also impair antiviral immunity. We hypothesized that the Treg frequency and the Treg phenotype are altered in hepatitis C virus (HCV)-infected recipients of liver transplantation (LT) with possible prognostic implications. Tregs from 141 individuals, including healthy individuals, LT recipients with or without persistent HCV infections, and nontransplant patients with chronic HCV, were studied. A comprehensive phenotypic analysis was performed with multicolor flow cytometry, which included standard Treg markers [CD4 1 , CD25 hi , CD127 -, and FoxP3 1 in addition to HLA DR, CCR7, CD45RA, CD62L, CD49d, CD39, ICOS and LAP-TGFb stainings. Healthy individuals and LT patients displayed similar Treg frequencies and largely comparable Treg phenotypes, which were stable over time after transplantation. In contrast, Tregs with a CD45RA -CCR7 -effector phenotype were enriched in LT recipients with chronic HCV versus HCV-negative transplant patients. HCV infection, rather than LT, altered the expression of functional markers on Tregs. A principal component analysis revealed distinct Treg phenotypes in HCV-infected LT recipients with rejection and patients with recurrent graft HCV. In conclusion, Treg phenotypes are altered in HCV-infected LT patients. An investigation of Tregs may possibly help to distinguish recurrent HCV from graft rejection. Further functional studies are needed to define the role of Tregs in determining the balance between antiviral and allogenic immunity. Liver Transpl 21:381-395, 2015. V C 2015 AASLD.

Distinct Immune Imprints of Post–Liver Transplantation Hepatitis C Persist Despite Viral Clearance

“…( 43‐47 ) Our group has previously demonstrated that Treg phenotypes such as the expression of human leukocyte antigen – DR isotope may differentiate rejection from recurrent HCV infection. ( 20 ) However, we could not study this further in this study because none of the patients experienced biopsy‐proven rejection episodes.…”

Prospective evaluation of immune haemolysis in liver transplantation

“…Furosemide has been associated with positive DAT, without haemolysis . Also, HCV infection is associated with numerous immunological diseases, although the occurrence of haemolysis is rare . Furthermore, positive DAT with negative eluate may be secondary to non‐specific adsorption of IgG in the RBCs, which is associated with liver disease .…”

Purinergic Profiling of Regulatory T-cells in Patients With Episodic Migraine

“…Different classifications of Tregs are used in clinical studies based on their expression of various functional antigens ( Sakaguchi et al, 2010 ; Gronert et al, 2015 ; Ambada et al, 2017 ). In our work we identified subsets of Tregs based on their expression of CD45R0 and CD62L, as outlined by previous studies ( Sakaguchi et al, 2010 ; Gronert et al, 2015 ; Ambada et al, 2017 ). Out of the four main Treg subsets – ‘naïve’, CM, EM, and TEMRA – we found that the last two were significantly higher in the peripheral blood of migraine patients.…”

“…Tregs were characterized by the expression of CD3, CD4 and high levels of the IL-2R alpha chain (CD25high). T cell differentiation subsets were defined based on expression pattern of CD45R0 and CD62L as ‘naïve’ (N, CD45R0–CD62L+), central memory (CM, CD45R0+CD62L+), effector memory (EM, CD45R0+CD62L–), and terminally differentiated CD45RA-positive effector T-cells (TEMRA, CD45R0–CD62L–) ( Gronert et al, 2015 ; Ambada et al, 2017 ). The expression of CD39 and CD73 was evaluated in all above mentioned T-cell subsets.…”