The biology of Epstein–Barr virus in post‐transplant lymphoproliferative disease

Abstract

Post-transplant lymphoproliferative disease (PTLD) is a B cell proliferative disorder that is associated with Epstein-Barr virus (EBV), an ubiquitous herpesvirus. EBV-seronegative organ transplant recipients are at highest risk. EBV infection in PTLD lesions exists in a latent rather than lytic state, making tumor regression in response to antiviral agents unlikely. Viral latency proteins drive proliferation of T cells but also allow T cells to target PTLD lesions for destruction. Augmentation of the cellular immune response via the infusion of EBV-specific cytotoxic T cells has yielded promising results in the prevention and treatment of PTLD in bone marrow transplant recipients. Efforts to extend this strategy to solid organ transplant recipients are ongoing.

Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation: similarity to human PTLD and association with a porcine gammaherpesvirus

“…8,9 In human transplant recipients, PTLD is generally associated with the intensity of immune suppression, particularly the use of antilymphocyte preparations, with primary EBV infection, and with coinfection by cytomegalovirus. 6 The high incidence in the miniature swine model may be related to the absence of WBI or other myelosuppressive treatments in this protocol. We have not observed PTLD or lymphoma in animals treated under any other transplantation protocol used for miniature swine, including a similar preparative regimen for PBSC transplantation that differs only in the addition of 300 cGy WBI.…”

“…4,5 A strong correlation has been reported between B-cell neoplasms developing in immunosuppressed patients and the presence of the Blymphotropic gammaherpesvirus Epstein-Barr virus (EBV). 6 In humans, PTLD is thought to represent a spectrum of EBV-driven lymphoid proliferations ranging in histologic appearance from a reactive polymorphic expansion of EBV-infected lymphocytes to monoclonal B-cell lymphomas. 7 Studies of patients who developed PTLD have implicated several risk factors, including T-cell depletion and the degree of immunosuppression; however, the pathogenesis of PTLD is not completely understood.…”

EBV-Associated Lymphoproliferative Disorders: Classification and Treatment

“…Both EBV and HHV-8 act predominantly through direct mechanisms, that is, the virus is able to directly infect the tumor clone and exerts a transforming effect upon B cells. Viral infection in PTLD exploits several strategies to ensure persistent infection, namely, prevention of death of infected cells, enhancement of their proliferation to maintain the infected reservoir, and evasion of the immune system [33][34][35]. Several lines of evidence suggest that EBV infection has a major pathogenetic role in PTLDs: (a) EBV infects ϳ60%-80% PTLD patients, including 100% of early-onset PTLD patients [6]; (b) in many cases of monomorphic PTLD, EBV infection is monoclonal, consistent with the hypothesis that the virus has been present in the tumor progenitor cell since the early phases of clonal expansion; (c) a decrease in EBV-specific cytotoxic T lymphocytes (CTLs) and an increase in the EBV viral load are strongly associated with PTLD development [36]; and (d) treatment of PTLDs with autologous EBV-specific CTLs results in viral load control and tumor size reduction.…”

The human T cell immune response to Epstein-Barr virus

“…In immunosuppressed individuals, such as transplant patients, primary EBV infection usually results in PTLD that often progress into B cell lymphomas£ (Hsieh et al, 1999, Paya et al, 1999, Hopwood and Crawford, 2000. Current prophylactic and therapeutic approaches for PTLD and lymphomas are far from optimal.…”