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Development of a Treatment Regimen for Human Cytomegalovirus (CMV) Infection in Bone Marrow Transplantation Recipients by Adoptive Transfer of Donor‐Derived CMV‐Specific T Cell Clones Expanded In Vitro a
Author(s) -
GREENBERG P. D.,
REUSSER P.,
GOODRICH J. M.,
RIDDELL S. R.
Publication year - 1991
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1991.tb33450.x
Subject(s) - cytomegalovirus , adoptive cell transfer , human cytomegalovirus , cytomegalovirus infection , betaherpesvirinae , in vitro , medicine , transplantation , immunology , bone marrow transplantation , virology , regimen , bone marrow , herpesviridae , virus , biology , pathology , t cell , immune system , viral disease , biochemistry
CMV infection represents a major cause of morbidity and mortality in immunosuppressed bone marrow transplant (BMT) recipients. Life-threatening CMV infection was found to occur only in patients who did not develop a CMV-specific CD8+ Tc response. Therefore, methods to clone and expand CMV-specific Tc were developed to facilitate analysis of the specificity of the CD8+ Tc response to CMV responsible for protective immunity in seropositive donors, and to permit adoptive transfer of in vitro expanded CMV-specific Tc derived from bone marrow donors into immunocompetent HLA-matched BMT recipients to augment resistance to CMV. The immunodominant class I-restricted Tc response present in healthy seropositive individuals was found to be specific for a conserved CMV antigen introduced into the cytoplasm and presented shortly following viral penetration and uncoating, and did not require endogenous viral gene expression and protein synthesis. Thus, the protective immune response to CMV mediates lysis of virally-infected cells prior to virion assembly. Processing of viral proteins and access to presentation in the context of class I MHC molecules immediately following infection of target cells was selective for internal virion proteins, such as the tegument protein pp65. By contrast, presentation by infected cells of GB, the major CMV envelope protein, or IE, the major regulatory protein, was delayed due to a requirement for endogenous synthesis in infected cells, and CD8+ Tc specific for these proteins were detected in low frequency as compared to the immundominant response.