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Human CD28-CD8+ T cells contain greatly expanded functional virus-specific memory CTL clones.
M P Weekes1, A J Carmichael, M R Wills
1Department of Medicine, University of Cambridge Clinical School, United Kingdom.
Journal of Immunology (Baltimore, Md. : 1950)
|June 8, 1999
Summary
As people age, CD8+ T cells lose CD28. This study found that CD28-CD8+ T cells in healthy individuals contain functional memory T cell clones specific for persistent viruses like HCMV and HIV.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- CD8+ T cells typically express CD28 at birth, but this expression declines with age.
- The Ag specificity and function of CD28-CD8+ T cells, particularly in persistent viral infections, remain largely undefined.
Purpose of the Study:
- To investigate the contribution of CD28-CD8+ T cells to the memory CD8+ cytotoxic T lymphocyte (CTL) response against human cytomegalovirus (HCMV) and human immunodeficiency virus (HIV).
Main Methods:
- Generated and sequenced TCR beta-chains of CTL clones specific for viral peptides from peripheral blood mononuclear cells (PBMC) of healthy virus carriers.
- Quantified CTL clone size using clonotypic oligonucleotides and assessed CTL precursor frequency via limiting dilution analysis.
Main Results:
- Virus-specific CTL clones were consistently more abundant in the CD28-CD8+ T cell population than in the overall CD8+ T cell population.
- High frequencies of functional memory CTL precursors specific for HCMV or HIV peptides were found within the CD28-CD8+ T cell subset.
Conclusions:
- Human CD28-CD8+ T cells harbor significant populations of functional, virus-specific memory CTL clones in asymptomatic HCMV and HIV infections.
- These findings highlight the importance of CD28- T cells in maintaining adaptive immunity against persistent viral threats.