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15 November 2006

Volume 194, Number 10
The Journal of Infectious Diseases 2006;194:1410–1421
© 2006 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2006/19410-0010$15.00
DOI: 10.1086/508495
MAJOR ARTICLE

Functional Comparison of T Cells Recognizing Cytomegalovirus pp65 and Intermediate‐Early Antigen Polypeptides in Hematopoietic Stem‐Cell Transplant and Solid Organ Transplant Recipients

Simon F. Lacey,1

Corinna La Rosa,1

Wendy Zhou,1

Madeva C. Sharma,1

Joy Martinez,1

Aparna Krishnan,1

Ghislaine Gallez‐Hawkins,2

Lia Thao,2

Jeff Longmate,3

Ricardo Spielberger,4

Stephen J. Forman,4

Ajit Limaye,5

John A. Zaia,2 and

Don J. Diamond1

1Laboratory of Vaccine Research, 2Division of Virology, and 3Department of Biostatistics, Division of Information Sciences, Beckman Research Institute of the City of Hope, and 4Department of Hematology and Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, California; 5Departments of Laboratory Medicine and Medicine, University of Washington, Seattle

The functional status of cytotoxic T lymphocyte (CTL) populations recognizing cytomegalovirus intermediate‐early antigen (IE1) and pp65 polypeptides was investigated in peripheral blood mononuclear cells from hematopoietic stem‐cell transplant (HSCT) and solid organ transplant recipients. Combined flow‐based CD107a/b degranulation/mobilization and intracellular cytokine (ICC) assays using peptide libraries as antigens indicated that a significantly higher proportion of pp65‐specific CTLs were in a more mature functional state, compared with IE1‐specific CTLs. Degranulation/multiple cytokine ICC assays also indicated that a significantly higher proportion of pp65‐specific than IE1‐specific CTLs secreted both interferon‐γ and tumor necrosis factor–α and possessed greater cytotoxic potential. These results support our earlier findings of functional differences between CTLs recognizing individual epitopes within the IE1 and pp65 antigens in healthy donors and HSCT recipients and extend them to a broader array of human leukocyte antigen–restricted responses to those antigens. We also provide evidence of a relationship between cytotoxic function and the ability of cytomegalovirus‐specific CTLs to secrete multiple cytokines.

Received 16 May 2006; accepted 18 July 2006; electronically published 11 October 2006.

Reprints or correspondence: Dr. Simon F. Lacey, Laboratory of Vaccine Research, Rm. 1001c, Fox South Blvd., Beckman Research Institute of the City of Hope, 1450 E. Duarte Rd., Duarte, CA 91010‐3000 ().

Cited by

W. Zhou, J. Longmate, S. F. Lacey, J. M. Palmer, G. Gallez-Hawkins, L. Thao, R. Spielberger, R. Nakamura, S. J. Forman, J. A. Zaia, D. J. Diamond. (2009) Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients. Blood 113:25, 6465-6476
Online publication date: 18-Jul-2009.
CrossRef
B Pourgheysari, K P Piper, A McLarnon, J Arrazi, R Bruton, F Clark, M Cook, P Mahendra, C Craddock, P A H Moss. (2009) Early reconstitution of effector memory CD4+ CMV-specific T cells protects against CMV reactivation following allogeneic SCT. Bone Marrow Transplantation 43:11, 853-861
Online publication date: 1-Jul-2009.
CrossRef
G. Nebbia, F. M. Mattes, C. Smith, E. Hainsworth, J. Kopycinski, A. Burroughs, P. D. Griffiths, P. Klenerman, V. C. Emery. (2009) Polyfunctional Cytomegalovirus-Specific CD4+ and pp65 CD8+ T Cells Protect Against High-Level Replication After Liver Transplantation. American Journal of Transplantation 8:12, 2590-2599
Online publication date: 1-Jan-2009.
CrossRef
Véronique Mersseman, Verena Böhm, Rafaela Holtappels, Petra Deegen, Uwe Wolfrum, Bodo Plachter, Sabine Reyda. (2008) Refinement of strategies for the development of a human cytomegalovirus dense body vaccine. Medical Microbiology and Immunology 197:2, 97-107
Online publication date: 1-Jul-2008.
CrossRef
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)
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
Online publication date: 1-Sep-2007.
CrossRef

  • Potential conflicts of interest: none reported.

    Financial support: National Institutes of Health (grants P01‐CA30206 to S.J.F., J.A.Z., and D.J.D.; R01‐CA77544 to D.J.D.; R01‐AI058148 to J.A.Z.; and M01‐RR00043‐38 in support of the General Clinical Research Center at City of Hope); Leukemia and Lymphoma Society (award 6122‐02 to S.F.L. and Comprehensive Cancer Center grant CA33572 to City of Hope); Edwin and Bea Wolfe Charitable Foundation (support to the Laboratory of Vaccine Research).

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