Quantitating the Magnitude of the Lymphocytic Choriomeningitis Virus-specific Cd8 T-cell Response: It is Even Bigger Than We Thought.
From: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Journal of virology
- Publish Date: Feb 2007
- ISSN: 0022-538X
- Volume: 81
- Issue: 4
- Pages: 2002-11
- Medium: Print
- Language: English
- Citation (JAMA): Masopust David, Murali-Krishna Kaja, Ahmed Rafi, et al. Quantitating the Magnitude of the Lymphocytic Choriomeningitis Virus-specific Cd8 T-cell Response: It is Even Bigger Than We Thought.. J. Virol. Feb 2007;81:2002-11
Abstract
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 > or =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.
Mesh Headings (Keywords): Animals, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Female, Lymphocyte Count, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Mice, Mice, Inbred C57BL, Species Specificity, Spleen
Check for Full Text / PubMed Unique Identifier (PMID): 17151096
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