Characterization of the CD4+ T Cell Response to Epstein-Barr Virus during Primary and Persistent Infection

doi:10.1084/jem.20022058

Published 15 September 2003. doi:10.1084/jem.20022058

This Article

	Full Text
	Full Text (PDF, 186K)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Amyes, E.
	Articles by Callan, M. F.C.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Amyes, E.
	Articles by Callan, M. F.C.

Social Bookmarking

	What's this?

© Rockefeller University Press, 0022-1007/2003/9/903 $5.00
The Journal of Experimental Medicine, Volume 198, Number 6, 903-911

Characterization of the CD4⁺ T Cell Response to Epstein-Barr Virus during Primary and Persistent Infection

Elisabeth Amyes¹, Chris Hatton², Damien Montamat-Sicotte¹, Nancy Gudgeon³, Alan B. Rickinson³, Andrew J. McMichael¹ and Margaret F.C. Callan¹

¹ Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine
² Department of Haematology, The John Radcliffe, OX3 9DS Oxford, United Kingdom
³ Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, B15 2TT Birmingham, United Kingdom

Address correspondence to Margaret Callan, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, OX3 9DS Oxford, United Kingdom. Phone: 44-1865-222448; Fax: 44-1865-222502; email: mcallan{at}molbiol.ox.ac.uk

The CD8⁺ T cell response to Epstein-Barr virus (EBV) is wellcharacterized. Much less is known about the evolution of theCD4⁺ T cell response. Here we show that EBV stimulates a primaryburst of effector CD4⁺ T cells and this is followed by a periodof down-regulation. A small population of EBV-specific effectorCD4⁺ T cells survives during the lifelong persistent phase ofinfection. The EBV-specific effector CD4⁺ T cells accumulatewithin a CD27⁺ CD28⁺ differentiation compartment during primaryinfection and remain enriched within this compartment throughoutthe persistent phase of infection. Analysis of CD4⁺ T cell responsesto individual epitopes from EBV latent and lytic cycle proteinsconfirms the observation that the majority of the effector cellsexpress both CD27 and CD28, although CD4⁺ T cells specific forlytic cycle antigens have a greater tendency to express CD45RAthan those specific for the latent antigens. In clear contrast,effector CD4⁺ T cells specific for cytomegalovirus (CMV) accumulatewithin the CD27^- CD28⁺ and CD27^- CD28^- compartments. There arestriking parallels in terms of the differentiation of CD8⁺ Tcells specific for EBV and CMV. The results challenge currentideas on the definition of memory subsets.

Key Words: immunity • antigens CD27 • antigens CD28 • Epstein-Barr virus • cytomegalovirus

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Jursik, C., Prchal, M., Grillari-Voglauer, R., Drbal, K., Fuertbauer, E., Jungfer, H., Albert, W. H., Steinhuber, E., Hemetsberger, T., Grillari, J., Stockinger, H., Katinger, H. (2009). Large-Scale Production and Characterization of Novel CD4+ Cytotoxic T Cells with Broad Tumor Specificity for Immunotherapy. Mol Cancer Res 7: 339-353 [Abstract] [Full Text]
Sattler, A., Wagner, U., Rossol, M., Sieper, J., Wu, P., Krause, A., Schmidt, W. A., Radmer, S., Kohler, S., Romagnani, C., Thiel, A. (2009). Cytokine-induced human IFN-{gamma}-secreting effector-memory Th cells in chronic autoimmune inflammation. Blood 113: 1948-1956 [Abstract] [Full Text]
Klein, G. (2009). Toward a genetics of cancer resistance. Proc. Natl. Acad. Sci. USA 106: 859-863 [Abstract] [Full Text]
Lunemann, J. D., Huppke, P., Roberts, S., Bruck, W., Gartner, J., Munz, C. (2008). BROADENED AND ELEVATED HUMORAL IMMUNE RESPONSE TO EBNA1 IN PEDIATRIC MULTIPLE SCLEROSIS. Neurology 71: 1033-1035 [Full Text]
Okada, R., Kondo, T., Matsuki, F., Takata, H., Takiguchi, M. (2008). Phenotypic classification of human CD4+ T cell subsets and their differentiation. Int Immunol 20: 1189-1199 [Abstract] [Full Text]
Pitard, V., Roumanes, D., Lafarge, X., Couzi, L., Garrigue, I., Lafon, M.-E., Merville, P., Moreau, J.-F., Dechanet-Merville, J. (2008). Long-term expansion of effector/memory V{delta}2- {gamma}{delta} T cells is a specific blood signature of CMV infection. Blood 112: 1317-1324 [Abstract] [Full Text]
Lunemann, J. D., Jelcic, I., Roberts, S., Lutterotti, A., Tackenberg, B., Martin, R., Munz, C. (2008). EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-{gamma} and IL-2. JEM 205: 1763-1773 [Abstract] [Full Text]
Lunemann, J. D., Frey, O., Eidner, T., Baier, M., Roberts, S., Sashihara, J., Volkmer, R., Cohen, J. I., Hein, G., Kamradt, T., Munz, C. (2008). Increased Frequency of EBV-Specific Effector Memory CD8+ T Cells Correlates with Higher Viral Load in Rheumatoid Arthritis. J. Immunol. 181: 991-1000 [Abstract] [Full Text]
Crompton, L., Khan, N., Khanna, R., Nayak, L., Moss, P. A. H. (2008). CD4+ T cells specific for glycoprotein B from cytomegalovirus exhibit extreme conservation of T-cell receptor usage between different individuals. Blood 111: 2053-2061 [Abstract] [Full Text]
Bhaduri-McIntosh, S., Rotenberg, M. J., Gardner, B., Robert, M., Miller, G. (2008). Repertoire and frequency of immune cells reactive to Epstein-Barr virus-derived autologous lymphoblastoid cell lines. Blood 111: 1334-1343 [Abstract] [Full Text]
Appay, V., Bosio, A., Lokan, S., Wiencek, Y., Biervert, C., Kusters, D., Devevre, E., Speiser, D., Romero, P., Rufer, N., Leyvraz, S. (2007). Sensitive Gene Expression Profiling of Human T Cell Subsets Reveals Parallel Post-Thymic Differentiation for CD4+ and CD8+ Lineages. J. Immunol. 179: 7406-7414 [Abstract] [Full Text]
Shiao, S. L., Kirkiles-Smith, N. C., Shepherd, B. R., McNiff, J. M., Carr, E. J., Pober, J. S. (2007). Human Effector Memory CD4+ T Cells Directly Recognize Allogeneic Endothelial Cells In Vitro and In Vivo. J. Immunol. 179: 4397-4404 [Abstract] [Full Text]
Rowe, M., Glaunsinger, B., van Leeuwen, D., Zuo, J., Sweetman, D., Ganem, D., Middeldorp, J., Wiertz, E. J. H. J., Ressing, M. E. (2007). Host shutoff during productive Epstein-Barr virus infection is mediated by BGLF5 and may contribute to immune evasion. Proc. Natl. Acad. Sci. USA 104: 3366-3371 [Abstract] [Full Text]
Heller, K. N., Upshaw, J., Seyoum, B., Zebroski, H., Munz, C. (2007). Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers. Blood 109: 1138-1146 [Abstract] [Full Text]
Casazza, J. P., Betts, M. R., Price, D. A., Precopio, M. L., Ruff, L. E., Brenchley, J. M., Hill, B. J., Roederer, M., Douek, D. C., Koup, R. A. (2006). Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation. JEM 203: 2865-2877 [Abstract] [Full Text]
Stubbe, M., Vanderheyde, N., Goldman, M., Marchant, A. (2006). Antigen-Specific Central Memory CD4+ T Lymphocytes Produce Multiple Cytokines and Proliferate In Vivo in Humans. J. Immunol. 177: 8185-8190 [Abstract] [Full Text]
Zaunders, J. J., Dyer, W. B., Munier, M. L., Ip, S., Liu, J., Amyes, E., Rawlinson, W., De Rose, R., Kent, S. J., Sullivan, J. S., Cooper, D. A., Kelleher, A. D. (2006). CD127+CCR5+CD38+++ CD4+ Th1 Effector Cells Are an Early Component of the Primary Immune Response to Vaccinia Virus and Precede Development of Interleukin-2+ Memory CD4+ T Cells.. J. Virol. 80: 10151-10161 [Abstract] [Full Text]
Zaunders, J. J., Ip, S., Munier, M. L., Kaufmann, D. E., Suzuki, K., Brereton, C., Sasson, S. C., Seddiki, N., Koelsch, K., Landay, A., Grey, P., Finlayson, R., Kaldor, J., Rosenberg, E. S., Walker, B. D., Fazekas de St. Groth, B., Cooper, D. A., Kelleher, A. D., on Behalf of the PHAEDRA Study Team, (2006). Infection of CD127+ (Interleukin-7 Receptor+) CD4+ Cells and Overexpression of CTLA-4 Are Linked to Loss of Antigen-Specific CD4 T Cells during Primary Human Immunodeficiency Virus Type 1 Infection.. J. Virol. 80: 10162-10172 [Abstract] [Full Text]
Seddiki, N., Santner-Nanan, B., Tangye, S. G., Alexander, S. I., Solomon, M., Lee, S., Nanan, R., de Saint Groth, B. F. (2006). Persistence of naive CD45RA+ regulatory T cells in adult life. Blood 107: 2830-2838 [Abstract] [Full Text]
Genova, G. D., Roddick, J., McNicholl, F., Stevenson, F. K. (2006). Vaccination of human subjects expands both specific and bystander memory T cells but antibody production remains vaccine specific. Blood 107: 2806-2813 [Abstract] [Full Text]
Yuan, J., Cahir-McFarland, E., Zhao, B., Kieff, E. (2006). Virus and Cell RNAs Expressed during Epstein-Barr Virus Replication. J. Virol. 80: 2548-2565 [Abstract] [Full Text]
Landais, E., Saulquin, X., Bonneville, M., Houssaint, E. (2005). Long-Term MHC Class II Presentation of the EBV Lytic Protein BHRF1 by EBV Latently Infected B Cells following Capture of BHRF1 Antigen. J. Immunol. 175: 7939-7946 [Abstract] [Full Text]
Fletcher, J. M., Vukmanovic-Stejic, M., Dunne, P. J., Birch, K. E., Cook, J. E., Jackson, S. E., Salmon, M., Rustin, M. H., Akbar, A. N. (2005). Cytomegalovirus-Specific CD4+ T Cells in Healthy Carriers Are Continuously Driven to Replicative Exhaustion. J. Immunol. 175: 8218-8225 [Abstract] [Full Text]
Scriba, T. J., Purbhoo, M., Day, C. L., Robinson, N., Fidler, S., Fox, J., Weber, J. N., Klenerman, P., Sewell, A. K., Phillips, R. E. (2005). Ultrasensitive Detection and Phenotyping of CD4+ T Cells with Optimized HLA Class II Tetramer Staining. J. Immunol. 175: 6334-6343 [Abstract] [Full Text]
Fritsch, R. D., Shen, X., Sims, G. P., Hathcock, K. S., Hodes, R. J., Lipsky, P. E. (2005). Stepwise Differentiation of CD4 Memory T Cells Defined by Expression of CCR7 and CD27. J. Immunol. 175: 6489-6497 [Abstract] [Full Text]
Amyes, E., McMichael, A. J., Callan, M. F. C. (2005). Human CD4+ T Cells Are Predominantly Distributed among Six Phenotypically and Functionally Distinct Subsets. J. Immunol. 175: 5765-5773 [Abstract] [Full Text]
Piriou, E., van Dort, K., Nanlohy, N. M., van Oers, M. H. J., Miedema, F., van Baarle, D. (2005). Loss of EBNA1-specific memory CD4+ and CD8+ T cells in HIV-infected patients progressing to AIDS-related non-Hodgkin lymphoma. Blood 106: 3166-3174 [Abstract] [Full Text]
Zaunders, J. J., Munier, M. L., Kaufmann, D. E., Ip, S., Grey, P., Smith, D., Ramacciotti, T., Quan, D., Finlayson, R., Kaldor, J., Rosenberg, E. S., Walker, B. D., Cooper, D. A., Kelleher, A. D., on behalf of the PHAEDRA Study Team, (2005). Early proliferation of CCR5+ CD38+++ antigen-specific CD4+ Th1 effector cells during primary HIV-1 infection. Blood 106: 1660-1667 [Abstract] [Full Text]
Gross, A. J., Hochberg, D., Rand, W. M., Thorley-Lawson, D. A. (2005). EBV and Systemic Lupus Erythematosus: A New Perspective. J. Immunol. 174: 6599-6607 [Abstract] [Full Text]
Gudgeon, N. H., Taylor, G. S., Long, H. M., Haigh, T. A., Rickinson, A. B. (2005). Regression of Epstein-Barr Virus-Induced B-Cell Transformation In Vitro Involves Virus-Specific CD8+ T Cells as the Principal Effectors and a Novel CD4+ T-Cell Reactivity. J. Virol. 79: 5477-5488 [Abstract] [Full Text]
Ponsonby, A.-L., van der Mei, I., Dwyer, T., Blizzard, L., Taylor, B., Kemp, A., Simmons, R., Kilpatrick, T. (2005). Exposure to Infant Siblings During Early Life and Risk of Multiple Sclerosis. JAMA 293: 463-469 [Abstract] [Full Text]
Weekes, M. P., Wills, M. R., Sissons, J. G. P., Carmichael, A. J. (2004). Long-Term Stable Expanded Human CD4+ T Cell Clones Specific for Human Cytomegalovirus Are Distributed in Both CD45RAhigh and CD45ROhigh Populations. J. Immunol. 173: 5843-5851 [Abstract] [Full Text]
van Leeuwen, E. M. M., Remmerswaal, E. B. M., Vossen, M. T. M., Rowshani, A. T., Wertheim-van Dillen, P. M. E., van Lier, R. A. W., ten Berge, I. J. M. (2004). Emergence of a CD4+CD28- Granzyme B+, Cytomegalovirus-Specific T Cell Subset after Recovery of Primary Cytomegalovirus Infection. J. Immunol. 173: 1834-1841 [Abstract] [Full Text]
Stebbing, J., Gazzard, B., Mandalia, S., Teague, A., Waterston, A., Marvin, V., Nelson, M., Bower, M. (2004). Antiretroviral Treatment Regimens and Immune Parameters in the Prevention of Systemic AIDS-Related Non-Hodgkin's Lymphoma. JCO 22: 2177-2183 [Abstract] [Full Text]
Wang, R., Epstein, J., Charoenvit, Y., Baraceros, F. M., Rahardjo, N., Gay, T., Banania, J.-G., Chattopadhyay, R., de la Vega, P., Richie, T. L., Tornieporth, N., Doolan, D. L., Kester, K. E., Heppner, D. G., Norman, J., Carucci, D. J., Cohen, J. D., Hoffman, S. L. (2004). Induction in Humans of CD8+ and CD4+ T Cell and Antibody Responses by Sequential Immunization with Malaria DNA and Recombinant Protein. J. Immunol. 172: 5561-5569 [Abstract] [Full Text]