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Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic
bone marrow transplantation: pattern of recovery and correlation with
cytomegalovirus infection and disease
P Reusser, SR Riddell, JD Meyers and PD Greenberg
Fred Hutchinson Cancer Research Center, Seattle.
The high rate of severe cytomegalovirus (CMV) disease after bone marrow
transplantation (BMT) is related to the profound immunodeficiency
posttransplant. Because cytotoxic T lymphocytes (CTL) have been implicated
in resistance to viral infections, we examined the restoration of the
CMV-specific CTL response in 20 patients who received bone marrow from
HLA-matched, CMV-seropositive donors. Blood specimens were obtained from
patients at 1, 2, and 3 months after BMT and from the donors on a single
occasion. Peripheral blood mononuclear cells were cocultured with
CMV-infected donor-derived fibroblasts for 2 weeks and then tested for
cytotoxicity against CMV-infected and uninfected autologous or
HLA-mismatched fibroblasts. Cytolytic activity was detected in all 20
donors, with specificity for autologous CMV- infected targets demonstrable
in 17 (median CMV-specific lysis at an effector:target ratio of 15:1 was
32%, range 18% to 83%). Specific lysis was mediated by CD8+, class
I-restricted T cells, as shown by inhibition with anti-class I monoclonal
antibody and by selective depletion of effector cells. By contrast,
CMV-specific CTL were detected in only 10 of 20 patients after BMT (median
lysis 29% at 3 months post-BMT). None of these 10 patients developed CMV
pneumonia, whereas 6 of the 10 patients with an undetectable CMV-specific
CTL response after BMT died with CMV pneumonia. These results demonstrate
that restoration of CMV-specific CTL responses may require an extended time
period after BMT in some patients, and that such patients are at increased
risk of developing severe CMV disease. Approaches to reconstitute CMV
immunity in BMT patients by adoptive transfer of CMV- specific CD8+ CTL
clones derived from the bone marrow donor are now being pursued.
Volume 78,
Issue 5,
pp. 1373-1380,
09/01/1991
Copyright © 1991 by The American Society of Hematology
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|
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|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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[Abstract]
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|
|
|
|
|
|
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E. Meijer, G. J. Boland, and L. F. Verdonck
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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July 15, 2003;
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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G. Otten, M. Schaefer, C. Greer, M. Calderon-Cacia, D. Coit, J. Kazzaz, A. Medina-Selby, M. Selby, M. Singh, M. Ugozzoli, et al.
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77(10):
6087 - 6092.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Boeckh, W. Leisenring, S. R. Riddell, R. A. Bowden, M.-L. Huang, D. Myerson, T. Stevens-Ayers, M. E. D. Flowers, T. Cunningham, and L. Corey
Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity
Blood,
January 15, 2003;
101(2):
407 - 414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. E. Cheng and P. D. Greenberg
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J. Immunol.,
November 1, 2002;
169(9):
4990 - 4997.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Khan, N. Shariff, M. Cobbold, R. Bruton, J. A. Ainsworth, A. J. Sinclair, L. Nayak, and P. A. H. Moss
Cytomegalovirus Seropositivity Drives the CD8 T Cell Repertoire Toward Greater Clonality in Healthy Elderly Individuals
J. Immunol.,
August 15, 2002;
169(4):
1984 - 1992.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. Emeny, C. M. Wheeler, K. U. Jansen, W. C. Hunt, T.-M. Fu, J. F. Smith, S. MacMullen, M. T. Esser, and X. Paliard
Priming of Human Papillomavirus Type 11-Specific Humoral and Cellular Immune Responses in College-Aged Women with a Virus-Like Particle Vaccine
J. Virol.,
June 27, 2002;
76(15):
7832 - 7842.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hebart, S. Daginik, S. Stevanovic, U. Grigoleit, A. Dobler, M. Baur, G. Rauser, C. Sinzger, G. Jahn, J. Loeffler, et al.
Sensitive detection of human cytomegalovirus peptide-specific cytotoxic T-lymphocyte responses by interferon-gamma -enzyme-linked immunospot assay and flow cytometry in healthy individuals and in patients after allogeneic stem cell transplantation
Blood,
May 15, 2002;
99(10):
3830 - 3837.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Holtappels, N. K. A. Grzimek, C. O. Simon, D. Thomas, D. Dreis, and M. J. Reddehase
Processing and Presentation of Murine Cytomegalovirus pORFm164-Derived Peptide in Fibroblasts in the Face of All Viral Immunosubversive Early Gene Functions
J. Virol.,
May 13, 2002;
76(12):
6044 - 6053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Einsele, E. Roosnek, N. Rufer, C. Sinzger, S. Riegler, J. Loffler, U. Grigoleit, A. Moris, H.-G. Rammensee, L. Kanz, et al.
Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy
Blood,
May 13, 2002;
99(11):
3916 - 3922.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kaur, C. L. Hale, B. Noren, N. Kassis, M. A. Simon, and R. P. Johnson
Decreased Frequency of Cytomegalovirus (CMV)-Specific CD4+ T Lymphocytes in Simian Immunodeficiency Virus-Infected Rhesus Macaques: Inverse Relationship with CMV Viremia
J. Virol.,
March 19, 2002;
76(8):
3646 - 3658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Junghanss, M. Boeckh, R. A. Carter, B. M. Sandmaier, M. B. Maris, D. G. Maloney, T. Chauncey, P. A. McSweeney, M.-T. Little, L. Corey, et al.
Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study
Blood,
March 15, 2002;
99(6):
1978 - 1985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Reusser, H. Einsele, J. Lee, L. Volin, M. Rovira, D. Engelhard, J. Finke, C. Cordonnier, H. Link, and P. Ljungman
Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation
Blood,
February 15, 2002;
99(4):
1159 - 1164.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. V. Spencer, K. M. Lockridge, P. A. Barry, G. Lin, M. Tsang, M. E. T. Penfold, and T. J. Schall
Potent Immunosuppressive Activities of Cytomegalovirus- Encoded Interleukin-10
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