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1 March 2007

Volume 195, Number 5
The Journal of Infectious Diseases 2007;195:633–644
© 2007 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19505-0007$15.00
DOI: 10.1086/511307
MAJOR ARTICLE

Longitudinal Assessment of Cytomegalovirus (CMV)–Specific Immune Responses in Liver Transplant Recipients at High Risk for Late CMV Disease

Corinna La Rosa,1,a

Ajit P. Limaye,3,a

Aparna Krishnan,1

Jeff Longmate,2 and

Don J. Diamond1

1Laboratory of Vaccine Research and 2Department of Biostatistics, Division of Information Sciences, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, California; 3University of Washington Medical Center, Seattle

Cytomegalovirus (CMV)–seronegative recipients (R−) of a liver transplant from CMV-positive donors (D+) are at high risk for developing late CMV disease after discontinuation of antiviral prophylaxis. Levels of viremia and CMV-specific interferon (IFN)–γ–producing CD4+ and IFN-γ–producing CD8+ T cell responses were prospectively measured from discontinuation of antiviral prophylaxis until 1 year after transplantation in 17 consecutive D+/R− patients. CMV loads of >1000 copies/mL were strongly associated with CMV disease in the 6 symptomatic patients. Despite immunosuppression, broadly diverse T cells specific for CMV lysate or peptide libraries spanning pp65 and immediate early (IE) 1 immunodominant CMV antigens developed in all patients. A vigorous CD8+ T cell response to pp65 and IE1 antigens characterized the D+/R− cohort. Unexpectedly, none of these responses were predictive of CMV disease or viremia. No significant lymphopenia or functional impairment of CMV-specific T cells was detected in the symptomatic patients, whose morbidity was resolved after antiviral treatment while measurable CMV immunity was maintained during the 1-year observation period.

Received 15 June 2006; accepted 29 August 2006; electronically published 22 January 2007.

Reprints or correspondence: Dr. Don J. Diamond, Laboratory of Vaccine Research, Fox South, Beckman Research Institute of the City of Hope, Duarte, CA 91010 ().

Cited by

G. Nebbia, F. M. Mattes, C. Smith, E. Hainsworth, J. Kopycinski, A. Burroughs, P. D. Griffiths, P. Klenerman, V. C. Emery. (2008) Polyfunctional Cytomegalovirus-Specific CD4+ and pp65 CD8+ T Cells Protect Against High-Level Replication After Liver Transplantation. American Journal of Transplantation
Online publication date: 1-Nov-2008.
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F. M. Mattes, A. Vargas, J. Kopycinski, E. G. Hainsworth, P. Sweny, G. Nebbia, A. Bazeos, M. Lowdell, P. Klenerman, R. E. Phillips, P. D. Griffiths, V. C. Emery. (2008) Functional Impairment of Cytomegalovirus Specific CD8 T Cells Predicts High-Level Replication After Renal Transplantation. American Journal of Transplantation 8:5, 990-999
Online publication date: 1-Jun-2008.
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A. Egli, O. Bergamin, B. Müllhaupt, J.D. Seebach, N.J. Mueller, H.H. Hirsch. (2008) Cytomegalovirus-associated chorioretinitis after liver transplantation: case report and review of the literature. Transplant Infectious Disease 10:1, 27-43
Online publication date: 1-Mar-2008.
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Mark A. Jacobson, Qi Xuan Tan, Valerie Girling, C. Poon, Mark Van Natta, Douglas A. Jabs, Margaret Inokuma, Holden T. Maecker, Barry Bredt, and Elizabeth Sinclair, for the Studies of Ocular Complications of AIDS Research Group. (2008) Poor Predictive Value of Cytomegalovirus (CMV)–Specific T Cell Assays for the Development of CMV Retinitis in Patients with AIDS. Clinical Infectious Diseases 46:3, 458-466
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Abstract-Full Text-PDF Version (316 kB)
Corinna La Rosa, Aparna Krishnan, Jeff Longmate, Joy Martinez, Pooja Manchanda, Simon F. Lacey, Ajit P. Limaye, and Don J. Diamond. (2008) Programmed Death–1 Expression in Liver Transplant Recipients as a Prognostic Indicator of Cytomegalovirus Disease. The Journal of Infectious Diseases 197:1, 25-33
Online publication date: 1-Jan-2008.
Abstract-Full Text-PDF Version (400 kB)
Pascal R Meylan, Oriol Manuel. (2007) Late-onset cytomegalovirus disease in patients with solid organ transplant. Current Opinion in Infectious Diseases 20:4, 412-418
Online publication date: 1-Sep-2007.
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D. Lilleri, P. Zelini, C. Fornara, G. Comolli, G. Gerna. (2007) Inconsistent Responses of Cytomegalovirus-Specific T Cells to pp65 and IE-1 versus Infected Dendritic Cells in Organ Transplant Recipients. American Journal of Transplantation 7:8, 1997-2005
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Michael Boeckh and Stanley R. Riddell. (2007) Immunologic Predictors of Late Cytomegalovirus Disease after Solid Organ Transplantation—An Elusive Goal?. The Journal of Infectious Diseases 195:5, 615-617
Online publication date: 1-Mar-2007.
Citation-Full Text-PDF Version (164 kB)

  • Potential conflicts of interest: none reported.

    Financial support: These studies have been partially supported by grants from the National Cancer Institute (NCI; grants RO1-CA77544 and PO1-CA30206, Project III) and a subcontract from AI52065 to D.J.D. The City of Hope Comprehensive Cancer Center is supported by the NCI (grant CA33572). The Laboratory of Vaccine Research is partially supported by the Edwin and Bea Wolfe Charitable Foundation. Support for the City of Hope General Clinical Research Center (GCRC; satellite of the University of Southern California GCRC) is provided by the National Institutes of Health (grant MO1-RR0043-38).

  • (See the editorial commentary by Boeckh and Riddell, on pages 615–7.)

  • aC.L.R. and A.P.L. contributed equally to this work and should be considered co–first authors.

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