Rapid reconstitution of Epstein-Barr virus-specific T lymphocytes following allogeneic stem cell transplantation.
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. (Blood. 2000;96:2814-2821)
Marshall
N A
NA
Department of Medicine, Yale School of Medicine, New Haven, CT, USA.
Howe
J G
JG
Formica
R
R
Krause
D
D
Wagner
J E
JE
Berliner
N
N
Crouch
J
J
Pilip
I
I
Cooper
D
D
Blazar
B R
BR
Seropian
S
S
Pamer
E G
EG
D000328:Adult; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D001704:Biopolymers; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002648:Child; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005240:Feasibility Studies; D005260:Female; D006085:Graft Survival; D015789:HLA-A2 Antigen / Q000276:immunology; D015793:HLA-B7 Antigen / Q000276:immunology; D015795:HLA-B8 Antigen / Q000276:immunology; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000302:isolation & purification; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000517:prevention & control / Q000821:virology; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000276:immunology*; D019562:Viral Load; D001613:beta 2-Microglobulin / Q000276:immunology
D000956:Antigens, Viral; D001704:Biopolymers; D015789:HLA-A2 Antigen; D015793:HLA-B7 Antigen; D015795:HLA-B8 Antigen; D046911:Macromolecular Substances; D001613:beta 2-Microglobulin