Human CD28-CD8+ T cells contain greatly expanded functional virus-specific memory CTL clones

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.