T-Cell Responses to EBV

Hislop, Andrew D.; Taylor, Graham S.

doi:10.1007/978-3-319-22834-1_11

Cited by 27 publications

(39 citation statements)

References 162 publications

(205 reference statements)

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“…Patients suffering from these genetic diseases exhibit a specific susceptibility to EBV‐driven lymphoproliferative disorders, which is very often the most severe phenotype associated with these conditions, even though some patients can develop other infections particularly in CTPS1 deficiency. Like CTPS1, CD70, and CD27, RASGRP1 appears to be critical for expansion of T cells that needs to be particularly intense and sustained during EBV infection (Hislop & Taylor, ; Taylor et al , ). In T cells, CTPS1 expression is rapidly upregulated in response to TCR stimulation and inhibitors of the MAPK pathway strongly diminished the expression of CTPS1 (Martin et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, we failed to detect any expression of RASGRP1 Ala638GlyfsX16 in cells of the patient. In any case, abnormalities in effector functions may not play a determinant role in the susceptibility to EBV associated with the RASGRP1 deficiency since proliferation and expansion of activated T cells, which precede the effector phase of the immune response are impaired in RASGRP1‐deficient patients (Hislop & Taylor, ; Taylor et al , ). However, the two patients also exhibited T‐cell and NK‐cell lymphopenia with decreased naïve T cells indicative of impaired thymic development leading to decreased production of mature naïve T cells that is often observed in combined immunodeficiencies caused by gene defects affecting T‐cell signaling components (Notarangelo, ).…”

Section: Discussionmentioning

confidence: 99%

“…During Epstein–Barr virus infection, sustained expansion and differentiation of virus‐specific cytotoxic effector T cells are key steps to efficiently control virus‐infected cells (Hislop & Taylor, ; Taylor et al , ). Specific‐CD8 + T cells can represent more than 30% of circulating T cells during the primary infection, and this strong expansion is necessary to eliminate proliferating EBV‐infected B cells.…”

Section: Introductionmentioning

confidence: 99%

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Loss of RASGRP 1 in humans impairs T‐cell expansion leading to Epstein‐Barr virus susceptibility

et al. 2018

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Inherited CTPS1, CD27, and CD70 deficiencies in humans have revealed key factors of T‐lymphocyte expansion, a critical prerequisite for an efficient immunity to Epstein–Barr virus (EBV) infection. RASGRP1 is a T‐lymphocyte‐specific nucleotide exchange factor known to activate the pathway of MAP kinases (MAPK). A deleterious homozygous mutation in RASGRP1 leading to the loss RASGRP1 expression was identified in two siblings who both developed a persistent EBV infection leading to Hodgkin lymphoma. RASGRP1‐deficient T cells exhibited defective MAPK activation and impaired proliferation that was restored by expression of wild‐type RASGRP1. Similar defects were observed in T cells from healthy individuals when RASGRP1 was downregulated. RASGRP1‐deficient T cells also exhibited decreased CD27‐dependent proliferation toward CD70‐expressing EBV‐transformed B cells, a crucial pathway required for expansion of antigen‐specific T cells during anti‐EBV immunity. Furthermore, RASGRP1‐deficient T cells failed to upregulate CTPS1, an important enzyme involved in DNA synthesis. These results show that RASGRP1 deficiency leads to susceptibility to EBV infection and demonstrate the key role of RASGRP1 at the crossroad of pathways required for the expansion of activated T lymphocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Loss of RASGRP 1 in humans impairs T‐cell expansion leading to Epstein‐Barr virus susceptibility

et al. 2018

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“…21,[23][24][25][26][27][28][29] In EBV and ADV infections, importance of T cell immunity against was also reported. [37][38][39] Therefore, if T cell immunity is found to be insufficient in patients with viral reactivation, adoptive immunotherapy to enhance T cell reconstitution could be an option to consider in order to treat or prevent the development of endorgan disease (Fig. 1).…”

Section: Importance Of T Cells Against Viral Infectionsmentioning

confidence: 99%

Immunotherapy for opportunistic infections: Current status and future perspectives

Fuji¹,

Löffler

Einsele

et al. 2016

Virulence

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The outcome after allogeneic haematopoietic stem cell transplantation (allo-HSCT) has significantly improved during the last decades. However, opportunistic infections such as viral and mold infections are still a major obstacle for cure. Within this field, adoptive T cell therapy against pathogens is a promising treatment approach. Recently, the techniques to develop T cell products including pathogen-specific T cells have been sophisticated and are now available in accordance to good manufacturing practice (GMP). Here, we aim to summarize current knowledge about adoptive T cell therapy against viral and mold infections.

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“…This deficit in T cell function seems to open a window for uncontrolled expansion of EBV-infected B cells. The importance of T cells in the control of EBV in healthy individuals has been well described (9). The enigma in the transplant scenario however, is that virtually all organ recipients receive chronic immunosuppression that targets T cells, and EBV infection is ubiquitous, yet only a subset of patients develops PTLD.…”

Section: Introductionmentioning

confidence: 99%

The Immune Response to Epstein Barr Virus and Implications for Posttransplant Lymphoproliferative Disorder

Martinez

Krams

2017

Transplantation

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Posttransplant lymphoproliferative disorder (PTLD) is a serious complication in organ transplant recipients and is most often associated with the Epstein Barr virus (EBV). EBV is a common gammaherpes virus with tropism for B lymphocytes and infection in immunocompetent individuals is typically asymptomatic and benign. However, infection in immunocompromised or immunosuppressed individuals can result in malignant B cell lymphoproliferations such as PTLD. EBV+ PTLD can arise following primary EBV infection, or because of reactivation of a prior infection, and represents a leading malignancy in the transplant population. The incidence of EBV+ PTLD is variable depending on the organ transplanted and whether the recipient has preexisting immunity to EBV but can be as high as 20%. It is generally accepted that impaired immune function due to immunosuppression is a primary cause of EBV+ PTLD. In this overview, we review the EBV life cycle and discuss our current understanding of the immune response to EBV in healthy, immunocompetent individuals, in transplant recipients, and in PTLD patients. We review the strategies that EBV utilizes to subvert and evade host immunity and discuss the implications for the development of EBV+ PTLD.

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T-Cell Responses to EBV

Cited by 27 publications

References 162 publications

Loss of RASGRP 1 in humans impairs T‐cell expansion leading to Epstein‐Barr virus susceptibility

Loss of RASGRP 1 in humans impairs T‐cell expansion leading to Epstein‐Barr virus susceptibility

Immunotherapy for opportunistic infections: Current status and future perspectives

The Immune Response to Epstein Barr Virus and Implications for Posttransplant Lymphoproliferative Disorder

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