Direct Visualization of Antigen-specific CD8+T Cells during the Primary Immune Response to Epstein-Barr Virus In Vivo
Open accessAbstract
Primary infection with virus can stimulate a vigorous cytotoxic T cell response. The magnitude of the antigen-specific component versus the bystander component of a primary T cell response remains controversial. In this study, we have used tetrameric major histocompatibility complex–peptide complexes to directly visualize antigen-specific cluster of differentration (CD)8+ T cells during the primary immune response to Epstein-Barr virus (EBV) infection in humans. We show that massive expansion of activated, antigen-specific T cells occurs during the primary response to this virus. In one individual, T cells specific for a single EBV epitope comprised 44% of the total CD8+ T cells within peripheral blood. The majority of the antigen-specific cells had an activated/memory phenotype, with expression of human histocompatibility leukocyte antigen (HLA) DR, CD38, and CD45RO, downregulation of CD62 leukocyte (CD62L), and low levels of expression of CD45RA. After recovery from AIM, the frequency of antigen-specific T cells fell in most donors studied, although populations of antigen-specific cells continued to be easily detectable for at least 3 yr.
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As a result of an immune challenge, responding T and B cells may expand transiently to very high numbers, sometimes more than 10% of all circulating T cells, but decline rapidly.
“As a result of an immune challenge, the responding T and B cells may expand transiently to very high numbers [65], sometimes more than 10% of all circulating T cells, but these decline rapidly as a result of activation-induced cell death and from attrition over a longer time period.”
From Evolution of the immune system in humans from infancy to old age (2015) · cites this paper as [65]
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- Authors
- Callan, M. F. C., Tan, L., Annels, N., Ogg, G. S., Wilson, J. D. K., O'Callaghan, C. A., Steven, N., McMichael, A. J., & Rickinson, A. B.
- Affiliations
- John Radcliffe Hospital (GB)
- From the *Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom; and the ‡Cancer Research Campaign Institute for Cancer Studies, University of Birmingham, Birmingham, B15 2TT, United Kingdom
- Corresponding author
- McMichael, A.J.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1998-05-04
- Volume
- 187
- Issue
- 9
- Pages
- 1395-1402
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2212279
- OpenAlex
- W2058001723
- Cited by
- 892
- References
- 26
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 16 · 2023: 16 · 2022: 13 · 2021: 14 · 2020: 17 · 2019: 10 · 2018: 14 · 2017: 17 · 2016: 15 · 2015: 20 · 2014: 14 · 2013: 13 · 2012: 19
- FWCI
- 35.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- Epstein-Barr virus, CD8+ T cells, primary immune response, cytotoxic T lymphocytes, antigen-specific T cell expansion, memory T cells, HLA-DR, CD38, CD45RO, L-selectin, CD45RA, T cell activation, acute infectious mononucleosis
- MeSH terms
- Epitopes, Herpesvirus 4, Human, Flow Cytometry, HLA Antigens, Humans, Infectious Mononucleosis, Major Histocompatibility Complex, Membrane Glycoproteins, Peptides, Time Factors, Down-Regulation, Antigens, CD, CD8-Positive T-Lymphocytes
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