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*
Cancer Research Campaign Institute for Cancer Studies and
Medical Research Council, Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom;
Medical Research Council Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom; and
University School of Medicine, Shigenobu, Ehime, Japan.
EBV infection in humans induces CD8+ T cell memory to
viral epitopes derived from both lytic and latent cycle Ags. We have
analyzed the relationship between the phenotype and function of the
memory pool of T cells specific for these Ags. Lytic epitope-specific
populations were heterogeneous in terms of CD45RO/RA and CD28
expression, whereas latent epitope-specific populations were uniformly
CD45RO+ and CD28+, consistent with the higher
antigenic challenge from lytic epitopes driving some memory cells
toward a CD45RA+, CD28- phenotype. However,
both types of memory population showed immediate epitope-specific
cytotoxicity and type 1 cytokine production in ex vivo assays.
Cytotoxic function was not associated with preactivated T cells, as
EBV-specific populations were negative for activation markers such as
CD69 or CD38, nor could cytotoxic function be ascribed to
CD27- or CD56+ subsets, as such cells were not
detected in EBV-specific memory. Furthermore, cytotoxicity was not
limited to CD45RA+ and/or CD28- fractions, but
also was observed in CD45RO+, CD28+ populations
in lytic and latent epitope-specific memory. Cytokine (IFN-
,
TNF-
) responses, measured by intracytoplasmic staining after peptide
stimulation, also were detectable in CD45RO+ and
RA+ subsets as well as CD28+ and
CD28- subsets. Of other markers that were heterogeneous in
both lytic and latent epitope populations, CCR7 gave the best
discrimination of functionality; thus, CCR7+ cells
consistently failed to give an IFN- or TNF- response, whereas
many CCR7- cells were responsive. Our data are consistent
with effector functions having a broad distribution among
phenotypically distinct subsets of "effector memory" cells that
have lost the CCR7 marker.
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J. J. Obar, S. G. Crist, D. C. Gondek, and E. J. Usherwood Different Functional Capacities of Latent and Lytic Antigen-Specific CD8 T Cells in Murine Gammaherpesvirus Infection J. Immunol., January 15, 2004; 172(2): 1213 - 1219. [Abstract] [Full Text] [PDF]
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I. Kang, T. Quan, H. Nolasco, S.-H. Park, M. S. Hong, J. Crouch, E. G. Pamer, J. G. Howe, and J. Craft Defective Control of Latent Epstein-Barr Virus Infection in Systemic Lupus Erythematosus J. Immunol., January 15, 2004; 172(2): 1287 - 1294. [Abstract] [Full Text] [PDF]
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M. Bajenoff and S. Guerder Homing to Nonlymphoid Tissues Is Not Necessary for Effector Th1 Cell Differentiation J. Immunol., December 15, 2003; 171(12): 6355 - 6362. [Abstract] [Full Text] [PDF]
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K. Bickham, K. Goodman, C. Paludan, S. Nikiforow, M. L. Tsang, R. M. Steinman, and C. Munz Dendritic Cells Initiate Immune Control of Epstein-Barr Virus Transformation of B Lymphocytes In Vitro J. Exp. Med., December 1, 2003; 198(11): 1653 - 1663. [Abstract] [Full Text] [PDF]
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D. M. Koelle, Z. Liu, C. L. McClurkan, R. C. Cevallos, J. Vieira, N. A. Hosken, C. A. Meseda, D. C. Snow, A. Wald, and L. Corey Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor PNAS, October 28, 2003; 100(22): 12899 - 12904. [Abstract] [Full Text] [PDF]
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M. S. Topp, S. R. Riddell, Y. Akatsuka, M. C. Jensen, J. N. Blattman, and P. D. Greenberg Restoration of CD28 Expression in CD28- CD8+ Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production J. Exp. Med., September 15, 2003; 198(6): 947 - 955. [Abstract] [Full Text] [PDF]
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A. M. Byers, C. C. Kemball, J. M. Moser, and A. E. Lukacher Cutting Edge: Rapid In Vivo CTL Activity by Polyoma Virus-Specific Effector and Memory CD8+ T Cells J. Immunol., July 1, 2003; 171(1): 17 - 21. [Abstract] [Full Text] [PDF]
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L. Santodonato, G. D'Agostino, R. Nisini, S. Mariotti, D. M. Monque, M. Spada, L. Lattanzi, M. Paola Perrone, M. Andreotti, F. Belardelli, et al. Monocyte-Derived Dendritic Cells Generated After a Short-Term Culture with IFN-{alpha} and Granulocyte-Macrophage Colony-Stimulating Factor Stimulate a Potent Epstein-Barr Virus-Specific CD8+ T Cell Response J. Immunol., May 15, 2003; 170(10): 5195 - 5202. [Abstract] [Full Text] [PDF]
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J. K. Sandberg, N. M. Fast, K. A. Jordan, S. N. Furlan, J. D. Barbour, G. Fennelly, J. Dobroszycki, H. M. L. Spiegel, A. Wiznia, M. G. Rosenberg, et al. HIV-Specific CD8+ T Cell Function in Children with Vertically Acquired HIV-1 Infection Is Critically Influenced by Age and the State of the CD4+ T Cell Compartment J. Immunol., April 15, 2003; 170(8): 4403 - 4410. [Abstract] [Full Text] [PDF]
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L. E. Gamadia, E. B. M. Remmerswaal, J. F. Weel, F. Bemelman, R. A. W. van Lier, and I. J. M. Ten Berge Primary immune responses to human CMV: a critical role for IFN-gamma -producing CD4+ T cells in protection against CMV disease Blood, April 1, 2003; 101(7): 2686 - 2692. [Abstract] [Full Text] [PDF]
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E. V. Ravkov, C. M. Myrick, and J. D. Altman Immediate Early Effector Functions of Virus-Specific CD8+CCR7+ Memory Cells in Humans Defined by HLA and CC Chemokine Ligand 19 Tetramers J. Immunol., March 1, 2003; 170(5): 2461 - 2468. [Abstract] [Full Text] [PDF]
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D. Zhang, P. Shankar, Z. Xu, B. Harnisch, G. Chen, C. Lange, S. J. Lee, H. Valdez, M. M. Lederman, and J. Lieberman Most antiviral CD8 T cells during chronic viral infection do not express high levels of perforin and are not directly cytotoxic Blood, January 1, 2003; 101(1): 226 - 235. [Abstract] [Full Text] [PDF]
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C.-L. Lin, W.-F. Lo, T.-H. Lee, Y. Ren, S.-L. Hwang, Y.-F. Cheng, C.-L. Chen, Y.-S. Chang, S. P. Lee, A. B. Rickinson, et al. Immunization with Epstein-Barr Virus (EBV) Peptide-pulsed Dendritic Cells Induces Functional CD8+ T-Cell Immunity and May Lead to Tumor Regression in Patients with EBV-positive Nasopharyngeal Carcinoma Cancer Res., December 1, 2002; 62(23): 6952 - 6958. [Abstract] [Full Text] [PDF]
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E. M. van Leeuwen, L. E. Gamadia, P. A. Baars, E. B. Remmerswaal, I. J. ten Berge, and R. A. van Lier Proliferation Requirements of Cytomegalovirus-Specific, Effector-Type Human CD8+ T Cells J. Immunol., November 15, 2002; 169(10): 5838 - 5843. [Abstract] [Full Text] [PDF]
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P. J. Dunne, J. M. Faint, N. H. Gudgeon, J. M. Fletcher, F. J. Plunkett, M. V. D. Soares, A. D. Hislop, N. E. Annels, A. B. Rickinson, M. Salmon, et al. Epstein-Barr virus-specific CD8+ T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential Blood, July 18, 2002; 100(3): 933 - 940. [Abstract] [Full Text] [PDF]
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 P C L Beverley Immunology of vaccination Br. Med. Bull., July 1, 2002; 62(1): 15 - 28. [Abstract] [Full Text] [PDF]
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H. Tomiyama, T. Matsuda, and M. Takiguchi Differentiation of Human CD8+ T Cells from a Memory to Memory/Effector Phenotype J. Immunol., June 1, 2002; 168(11): 5538 - 5550. [Abstract] [Full Text] [PDF]
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M. D. Catalina, J. L. Sullivan, R. M. Brody, and K. Luzuriaga Phenotypic and Functional Heterogeneity of EBV Epitope-Specific CD8+ T Cells J. Immunol., April 15, 2002; 168(8): 4184 - 4191. [Abstract] [Full Text] [PDF]
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V. Appay, L. Papagno, C. A. Spina, P. Hansasuta, A. King, L. Jones, G. S. Ogg, S. Little, A. J. McMichael, D. D. Richman, et al. Dynamics of T Cell Responses in HIV Infection J. Immunol., April 1, 2002; 168(7): 3660 - 3666. [Abstract] [Full Text] [PDF]
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M. Suresh, J. K. Whitmire, L. E. Harrington, C. P. Larsen, T. C. Pearson, J. D. Altman, and R. Ahmed Role of CD28-B7 Interactions in Generation and Maintenance of CD8 T Cell Memory J. Immunol., November 15, 2001; 167(10): 5565 - 5573. [Abstract] [Full Text] [PDF]
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A. D. Hislop, N. E. Annels, N. H. Gudgeon, A. M. Leese, and A. B. Rickinson Epitope-specific Evolution of Human CD8+ T Cell Responses from Primary to Persistent Phases of Epstein-Barr Virus Infection J. Exp. Med., April 1, 2002; 195(7): 893 - 905. [Abstract] [Full Text] [PDF]
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