Elevation of CD4+ Differentiated Memory T Cells Is Associated With Acute Cellular and Antibody-Mediated Rejection After Liver Transplantation

Gerlach, Undine; Vogt, Katrin; Schlickeiser, Stephan; Meisel, Christian; Streitz, Mathias; Kunkel, Désirée; Appelt, Christine; Ahrlich, Stefanie; Lachmann, Nils; Neuhaus, P.; Pascher, Andreas; Sawitzki, Birgit

doi:10.1097/tp.0b013e318290de18

Cited by 31 publications

(23 citation statements)

References 40 publications

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“…This could also explain the enhanced heterogeneity of the Temra samples, since their epigenetic imprint might have been specialized over time. Indeed, increased frequencies of Temra cells have e.g., been reported in response to persistent CMV infection (Derhovanessian et al, 2011) and in liver disease, where high Temra cell numbers represent a significant risk of organ rejection after organ transplantation (Gerlach et al, 2013b). In contrast, Tmem cells isolated from the bone marrow did not display a Temra-like epigenetic phenotype but were positioned between Tcm and Tem cells, indicating that they have preserved significant expansion and differentiation capacity.…”

Section: Discussionmentioning

confidence: 99%

Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

Durek¹,

Nordström²,

Gasparoni³

et al. 2016

Immunity

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185

192

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Section: Discussionmentioning

confidence: 99%

Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

Durek¹,

Nordström²,

Gasparoni³

et al. 2016

Immunity

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185

192

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“…Due to their high pro-inflammatory cytokine production potential, CD4 + memory T cells are key promoters of chronic inflammation when the physiological regulatory circuits fail. Therefore, it is not surprising that increased proportions and absolute numbers of T EM and also T EMRA cells have been observed in patients suffering from chronic inflammatory diseases (24,25).…”

Section: T CM Cells Circulate Between Blood and Lymphoid Compartmentsmentioning

confidence: 99%

Progressive change in expression of killer-like receptorsr and GPR56 expression defines the cytokine production potential of human CD4⁺ T memory cells

Truong

Schlickeiser

Vogt

et al. 2017

Preprint

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Memory T cells mount an accelerated response upon re-challenge but are heterogeneous in phenotype and function. Traditionally memory T cells were classified into central memory, effector memory and terminally differentiated effector memory (T EMRA ) cells based on expression of CCR7 and CD45RA. Functional heterogeneity even within these subsets demonstrated the need for more suitable markers. We applied bulk and single gene expression profiling of human CD4 + memory T cells and identified surface markers, KLRB1, KLRG1, GPR56 and KLRF1, allowing classification into "low", "high" or "exhausted" cytokine producers. In contrast to common understanding KLRG1 expression was not associated with exhaustion and highest production of multiple cytokines was observed in KLRB1 + KLRG1 + GPR56 + T cells. Only additional KLRF1expression was associated with a decline in cytokine production. The superiority of KLRF1 to define exhausted cytokine producers compared to classical T EMRA identification was best exemplified for intrahepatic T cells in patients with inflammatory liver diseases.

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“…However, these drugs are associated with a number of issues, including high costs and numerous side effects. In addition, chronic immune rejection is inevitable (3)(4)(5). A number of in vitro studies (6)(7)(8)(9) have reported that mesenchymal stem cells (MSCs) produce an immunosuppressive effect.…”

Section: Introductionmentioning

confidence: 99%

Immunological effect induced by mesenchymal stem cells in a rat liver transplantation model

Sun¹,

Li²,

Wen³

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the immunological effect induced by bone marrow mesenchymal stem cells (MSCs) in rats that had undergone an orthotopic liver transplantation (OLT). MSCs were isolated and cultured from the bone marrow tissue of Lewis rats. In total, 42 rat OLT models were established and equally distributed into three groups. Group A received an OLT only, group B were also intramuscularly injected with tacrolimus (FK506), while group C were not only administered FK506, but also received MSCs. On day 7 post-surgery, the blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were measured. In addition, pathological changes were observed in the liver, levels of immune cytokines, including transforming growth factor (TGF)-β 1 , interleukin (IL)-10 and IL-12, were determined using immunohistochemistry, MSC homing was assessed and the survival times of the patients were recorded. Liver function, as assessed by the levels of ALT, AST and TBIL, was shown to improve in group C when compared with groups B and A (both P<0.01). In addition, survival analysis revealed that the survival times in groups B (median, 44 days) and C (median, 63 days) were significantly longer compared with group A (median, 11 days; both P<0.01). The survival rate of group C was also higher compared with group B (P<0.01). Pathological examination demonstrated strong acute rejection in group A, a mild acute rejection in group B and the mildest reaction in group C. In addition, immunohistochemistry revealed that TGF-β 1 and IL-10 expression was stronger in groups C and B, with group C exhibiting more significant expression than group B. By contrast, expression levels of IL-12 in groups A, B and C were positive, weak-positive and negative, respectively. Therefore, postoperative immunosuppression induced by MSCs is important for the alleviation of immune rejection from recipient-to-graft, and may induce immune tolerance in rat OLT models.

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Elevation of CD4+ Differentiated Memory T Cells Is Associated With Acute Cellular and Antibody-Mediated Rejection After Liver Transplantation

Cited by 31 publications

References 40 publications

Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

Progressive change in expression of killer-like receptorsr and GPR56 expression defines the cytokine production potential of human CD4⁺ T memory cells

Immunological effect induced by mesenchymal stem cells in a rat liver transplantation model

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Elevation of CD4+ Differentiated Memory T Cells Is Associated With Acute Cellular and Antibody-Mediated Rejection After Liver Transplantation

Cited by 31 publications

References 40 publications

Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

Progressive change in expression of killer-like receptorsr and GPR56 expression defines the cytokine production potential of human CD4+ T memory cells

Immunological effect induced by mesenchymal stem cells in a rat liver transplantation model

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Progressive change in expression of killer-like receptorsr and GPR56 expression defines the cytokine production potential of human CD4⁺ T memory cells