Dynamics of T-bet and Eomes Expression By Virus-Specific CD8+ T-Cells During Primary Epstein-Barr Virus and Cytomegalovirus Infection in a Kidney Transplant Recipient.

Abstract Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening hyperinflammatory syndrome triggered by EBV infection. It often becomes relapsed or refractory (r/r), given that etoposide-based regimens cannot effectively clear the virus. r/r EBV-HLH is invariably lethal in adults without allogeneic hematopoietic stem cell transplantation. Here, we performed a retrospective analysis of 7 r/r EBV-HLH patients who were treated with nivolumab on a compassionate-use basis at West China Hospital. All 7 patients tolerated the treatment and 6 responded to it. Five of them achieved and remained in clinical complete remission with a median follow-up of 16 months (range, 11.4-18.9 months). Importantly, both plasma and cellular EBV-DNAs were completely eradicated in 4 patients. Single-cell RNA-sequencing analysis showed that HLH syndrome was associated with hyperactive monocytes/macrophages and ineffective CD8 T cells with a defective activation program. Nivolumab treatment expanded programmed death protein-1–positive T cells and restored the expression of HLH-associated degranulation and costimulatory genes in CD8 T cells. Our data suggest that nivolumab, as a monotherapy, provides a potential cure for r/r EBV-HLH, most likely by restoring a defective anti-EBV response.

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Leiomyoma in a Renal Allograft

Case Reports in Urology ◽

10.1155/2016/8394942 ◽

2016 ◽

Vol 2016 ◽

pp. 1-4

Author(s):

Yan Jun Li ◽

Amila Rohan Siriwardana ◽

James Lawrence Penn Symons ◽

Gordon Francis O’Neill ◽

Min Ru Qiu ◽

...

Keyword(s):

Smooth Muscle ◽

Renal Transplant ◽

Transplant Recipient ◽

Renal Transplant Recipient ◽

Kidney Transplant ◽

Epstein Barr Virus ◽

Renal Allograft ◽

Barr Virus ◽

Epstein Barr ◽

Adult Renal Transplant Recipient

Leiomyomas are smooth muscle tumours that are rarely found in the kidney. There is one report of a leiomyoma in a kidney transplant in a paediatric recipient. Here, we report an adult renal transplant recipient who developed an Epstein-Barr virus-positive leiomyoma in his allograft 15 years after transplantation. The patient was converted to everolimus for posttransplant immunosuppression management and there was no sign of progression over a year.

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Rapid reconstitution of Epstein-Barr virus–specific T lymphocytes following allogeneic stem cell transplantation

Blood ◽

10.1182/blood.v96.8.2814.h8002814_2814_2821 ◽

2000 ◽

Vol 96 (8) ◽

pp. 2814-2821 ◽

Cited By ~ 1

Author(s):

Natalie A. Marshall ◽

John Greg Howe ◽

Richard Formica ◽

Diane Krause ◽

John E. Wagner ◽

...

Keyword(s):

T Cells ◽

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

Cd8 T Cells ◽

Epstein Barr Virus ◽

Hla Class I ◽

Barr Virus ◽

Matched Sibling ◽

Epstein Barr

Epstein-Barr virus (EBV)–specific CD8 T lymphocytes are present at remarkably high frequencies in healthy EBV+individuals and provide protection from EBV-associated lymphoproliferative diseases. Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a commonly used therapy in which T-cell surveillance for EBV is temporarily disrupted. Herein, human leukocyte antigen (HLA) class I tetramers were used to investigate the reestablishment of the EBV-specific CD8 T-cell repertoire in patients following allo-PBSCT. CD8+ T cells specific for lytic and latent cycle–derived EBV peptides rapidly repopulate the periphery of matched sibling allo-PBSCT patients. The relative frequencies of T cells specific for different EBV peptides in transplantation recipients closely reflect those of their respective donors. Investigation of patients at monthly intervals following unmanipulated allo-PBSCT demonstrated that the frequency of EBV-specific T cells correlates with the number of EBV genome copies in the peripheral blood and that expansion of EBV-specific T-cell populations occurs even in the setting of immunosuppressive therapy. In contrast, patients undergoing T-cell–depleted or unrelated cord blood transplantation have undetectable EBV-specific T cells, even in the presence of Epstein-Barr viremia. The protective shield provided by EBV-specific CD8 T cells is rapidly established following unmanipulated matched sibling allo-PBSCT and demonstrates that HLA class I tetramers complexed with viral peptides can provide direct and rapid assessment of pathogen-specific immunity in this and other vulnerable patient populations.

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Epstein-Barr virus–specific CD8+ T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential

Blood ◽

10.1182/blood-2002-01-0160 ◽

2002 ◽

Vol 100 (3) ◽

pp. 933-940 ◽

Cited By ~ 102

Author(s):

Padraic J. Dunne ◽

Jeffery M. Faint ◽

Nancy H. Gudgeon ◽

Jean M. Fletcher ◽

Fiona J. Plunkett ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Epstein Barr Virus ◽

Acute Infection ◽

Target Cells ◽

Elderly Persons ◽

Effector Cells ◽

Barr Virus ◽

Epstein Barr ◽

Acute Infectious Mononucleosis

Abstract During acute infection, latent and lytic Epstein-Barr virus (EBV) epitope-specific CD8+ T cells have a CD45RO+CD45RA− phenotype. However, after resolution of the infection, a large proportion of these cells, particularly those specific for lytic viral epitopes, re-express the CD45RA molecule. The role of CD8+ CD45RA+ T cells in ongoing immunity to EBV and other viruses is unknown. We now demonstrate that, relative to their CD45RO+ counterparts, the EBV-specific CD8+ T cells that revert to CD45RA expression after acute infectious mononucleosis are not in cell cycle, have longer telomeres, and are more resistant to apoptosis partly because of increased Bcl-2 expression. However, the EBV-specific CD8+CD45RA+ T cells have shorter telomeres than the total CD8+ CD45RA+ T-cell pool and predominantly express low levels of the CCR7 chemokine receptor, indicating that they are not naive cells. In addition, EBV-specific CD8+CD45RA+ T cells can be induced to proliferate and exhibit potent cytotoxic activity against target cells loaded with specific peptide. Our results strongly suggest, therefore, that EBV-specific CD8+ CD45RA+ T cells represent a stabilized virus-specific memory pool and not terminally differentiated effector cells. The identification of mechanisms that enable stable virus-specific CD8+ T cells to persist after acute infection may lead to the enhancement of antiviral immunity in immunocompromised and elderly persons.

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