Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors.

Journal article

Human cytomegalovirus (HCMV) infection is largely asymptomatic in the immunocompetent host, but remains a major cause of morbidity in immunosuppressed individuals. Using the recently described technique of staining antigen-specific CD8(+) T cells with peptide-HLA tetrameric complexes, we have demonstrated high levels of antigen-specific cells specific for HCMV peptides and show that this may exceed 4% of CD8(+) T cells in immunocompetent donors. Moreover, by staining with tetramers in combination with antibodies to cell surface markers and intracellular cytokines, we demonstrate functional heterogeneity of HCMV-specific populations. A substantial proportion of these are effector cytotoxic T lymphocytes, as demonstrated by their ability to lyse peptide-pulsed targets in "fresh" killing assays. These data suggest that the immune response to HCMV is periodically boosted by a low level of HCMV replication and that sustained immunological surveillance contributes to the maintenance of host-pathogen homeostasis. These observations should improve our understanding of the immunobiology of persistent viral infection.

Authors: Gillespie, G; Wills, MR; Appay, V; O'Callaghan, C; Murphy, M

• Journal: Journal of virology
• Volume: 74
• Issue: 17
• Pages: 8140-8150
• Publication date: 2000-09-01
• DOI: 10.1128/jvi.74.17.8140-8150.2000
• EISSN: 1098-5514
• ISSN: 0022-538X
• Language: English
• Keywords: CD8-Positive T-Lymphocytes; Cytomegalovirus Infections; T-Lymphocytes, Cytotoxic; Humans; Cytomegalovirus; Serologic Tests; Cytotoxicity, Immunologic; Phenotype; Immunocompetence; Histocompatibility Testing