Large clonal expansions of human virus‐specific memory cytotoxic T lymphocytes within the CD57+ CD28– CD8+ T‐cell population

Abstract

The proportion of human peripheral blood CD8⁺ T cells that are CD57⁺ CD28^– is low at birth but increases with age and in individuals infected with human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV). These CD57⁺ CD28^– CD8⁺ T cells contain large oligoclonal T-cell expansions whose antigen specificity is unknown. We identified clonal expansions of virus-specific memory cytotoxic T-lymphocyte precursors (CTLp) in both healthy carriers of HCMV and in asymptomatic HIV-infected subjects. In each subject, from the T-cell receptor (TCR) β-chain hypervariable sequence of each immunodominant CTL clone, we designed complementary oligonucleotide probes to quantify the size and phenotypic segregation of individual virus-specific CTL clones in highly purified populations of peripheral blood CD8⁺ T cells. We found large clonal expansions of virus-specific CTL clonotypes in CD57⁺ CD28^– CD8⁺ T cells. Using limiting dilution analysis, we found functional peptide-specific CTLp at high frequency in CD57⁺ CD28^– cells. Thus, memory CTL specific for persistent viruses account for many oligoclonal expansions within CD57⁺ CD28^– CD8⁺ T cells.