Quantitating the Magnitude of the Lymphocytic Choriomeningitis Virus-Specific CD8 T-Cell Response: It Is Even Bigger than We Thought
Open accessAbstract
Measuring the magnitudes and specificities of antiviral CD8 T-cell responses is critical for understanding the dynamics and regulation of adaptive immunity. Despite many excellent studies, the accurate measurement of the total CD8 T-cell response directed against a particular infection has been hampered by an incomplete knowledge of all CD8 T-cell epitopes and also by potential contributions of bystander expansion among CD8 T cells of irrelevant specificities. Here, we use several techniques to provide a more complete accounting of the CD8 T-cell response generated upon infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV). Eight days following infection, we found that 85 to 95% of CD8 T cells exhibit an effector phenotype as indicated by granzyme B, 1B11, CD62L, CD11a, and CD127 expression. We demonstrate that CD8 T-cell expansion is due to cells that divide >7 times, whereas heterologous viral infections only elicited <3 divisions among bystander memory CD8 T cells. Furthermore, we found that approximately 80% of CD8 T cells in spleen were specific for ten different LCMV-derived epitopes at the peak of primary infection. These data suggest that following a single LCMV infection, effector CD8 T cells divide ≥15 times and account for at least 80%, and possibly as much as 95%, of the CD8 T-cell pool. Moreover, the response targeted a very broad array of peptide major histocompatibility complexes (MHCs), even though we examined epitopes derived from only two of the four proteins encoded by the LCMV genome and C57BL/6 mice only have two MHC class I alleles. These data illustrate the potential enormity, specificity, and breadth of CD8 T-cell responses to viral infection and demonstrate that bystander activation does not contribute to CD8 T-cell expansion.
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During an ongoing immune response, activation markers such as CD11a and CD49d can be used to directly identify Ag-experienced CD8 T cells immediately ex vivo.
“Additionally, during an ongoing immune response, activation markers such as CD11a and CD49d [235], as well as markers of proliferation (BrdU or Ki67) (see section IV.5 Adoptive T cell transfers as a read-out for Ag-specific immune responses in mice) can be used to directly identify Ag-experienced CD8 T cells immediately ex vivo.”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [235]
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- Authors
- Masopust, D., Murali-Krishna, K., & Ahmed, R.
- Affiliations
- Emory University (US)
- Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
- Corresponding author
- Ahmed, Rafi
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2007-02-15
- Volume
- 81
- Issue
- 4
- Pages
- 2002-2011
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC1797597
- OpenAlex
- W2102032807
- Cited by
- 114
- References
- 61
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 10 · 2013: 8 · 2012: 7
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01ai30048-10-0-1)
- National Institute of Allergy and Infectious Diseases (P01AI044644, N01 AI030048, AI44644, AI 30048, U19AI044644)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- lymphocytic choriomeningitis virus, CD8+ T cells, antiviral T cell responses, effector T cell expansion, bystander activation, T cell epitopes, MHC class I restriction, T cell division, granzyme B, memory CD8+ T cells, viral infection
- MeSH terms
- Animals, Female, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Mice, Inbred C57BL, Species Specificity, Spleen, CD8-Positive T-Lymphocytes, Lymphocyte Count, Epitopes, T-Lymphocyte, Mice
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