Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients.
Reconstitution of cytomegalovirus (CMV)-specific CD8(+) T cells is essential to the control of CMV infection in CMV-positive recipients (R(+)) after allogeneic hematopoietic stem cell transplantation (HCT). Six-color flow cytometry was used to assess the functional profile of CMV-specific CD8(+) T cells in 62 of 178 R(+) HCT recipients followed virologically for CMV reactivation. R(+) recipients receiving grafts from CMV-negative donors (D(-); D(-)/R(+)) reconstituted fewer multifunctional CD8(+) T cells expressing tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1beta (MIP-1beta), and CD107 in addition to interferon-gamma (IFN-gamma), compared with D(+)/R(+) recipients. Unlike monofunctional CD8(+) T cells secreting IFN-gamma, which were abundantly generated during CMV reactivation in D(-)/R(+) recipients, the relative lack of multifunctional CD8(+) T cells persisted until at least 1 year post-HCT. D(-)/R(+) recipients were more likely to require recurrent and prolonged use of antivirals. These findings were robust to statistical adjustment for pretransplant factors, as well as for posttransplant factors including graft-versus-host disease (GVHD) and its treatment by steroids. These analyses suggest that D(+)/R(+) transplants, on average, generate higher levels of multifunctional CMV-specific T cells and require less antiviral therapy compared with D(-)/R(+) HCT recipients. These results highlight the benefit of D(+) donors in improving outcomes of R(+) HCT recipients by reducing the duration and recurrent need of antiviral treatment, aided by increased levels of multifunctional CMV-specific T cells.
Department of Virology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Wendi
W
Zhou
Jeff
J
Longmate
Simon F
SF
Lacey
Joycelynne M
JM
Palmer
Ghislaine
G
Gallez-Hawkins
Lia
L
Thao
Ricardo
R
Spielberger
Ryotaro
R
Nakamura
Stephen J
SJ
Forman
John A
JA
Zaia
Don J
DJ
Diamond
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000706:statistics & numerical data*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000302:isolation & purification* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology / Q000635:transmission; D022482:Cytomegalovirus Vaccines; D018562:Disease Transmission, Infectious; D005260:Female; D006085:Graft Survival / Q000276:immunology; D019337:Hematologic Neoplasms / Q000097:blood / Q000276:immunology / Q000601:surgery; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000706:statistics & numerical data*; D010750:Phosphoproteins / Q000276:immunology; D035781:Siblings; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000706:statistics & numerical data*; D016896:Treatment Outcome; D014763:Viral Matrix Proteins / Q000276:immunology; D014775:Virus Activation
D000998:Antiviral Agents; D016207:Cytokines; D022482:Cytomegalovirus Vaccines; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa