Epstein-Barr virus, rapamycin, and host immune responses.
OBJECTIVE
To summarize recent advances that contribute to our understanding of the pathobiology of Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease (PTLD), the host immune response to virally infected B cells, and the molecular basis for the effects of mammalian target of rapamycin inhibitors on EBV+ B-cell lymphomas.


RESULTS
Cytogenetic and genomic analyses support the concept that the underlying biology of EBV-associated PTLD is complex. Transplant recipients can generate and maintain significant populations of EBV-specific CD8+ memory T cells but the function of these cells may be impaired. EBV invokes multiple strategies to subvert and evade the host immune response. The phosphoinositide-3 kinase/Akt/mammalian target of rapamycin signal transduction pathway is a nexus for growth and survival signals in PTLD-associated EBV+ B-cell lymphomas.


CONCLUSIONS
Multiple factors influence the development of EBV-associated PTLD including the host immune response to EBV, virally induced effects on the infected cell and the host immune system, and the type and intensity of immunosuppression.
Krams
Sheri M
SM
Department of Surgery, Division of Transplantation, Stanford University School of Medicine, Stanford, California 94305-5492, USA.
Martinez
Olivia M
OM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016377:Organ Transplantation / Q000009:adverse effects*; D011494:Protein Kinases / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000821:virology; D058570:TOR Serine-Threonine Kinases
D007166:Immunosuppressive Agents; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus