Presence of effector CD8+ T cells in hepatitis C virus-exposed healthy seronegative donors

Paola Scognamiglio, Daniele Accapezzato, Marco Antonio Casciaro, Antonella Cacciani, Marco Artini, Guglielmo Bruno, Maria Lucia Chircu, John Sidney, Scott Southwood, Sergio Abrignani, Alessandro Sette, Vincenzo Barnaba

Research output: Contribution to journalArticle

Abstract

CTL responses against multiple hepatitis C virus (HCV) epitopes were detected in 7 of 29 (24.1%) healthy family members (HFM) persistently exposed to chronically HCV-infected patients (HCV-HFM). These precursor CTL were at very low or undetectable frequencies, as determined by limiting dilution analysis. However, when HCV-specific effector CD8+ T cells, freshly isolated from PBMC of HCV-HFM, were assessed by a sensitive enzyme-linked immunospot assay, their frequencies were several-fold higher than those of precursor CTL. These results indicate that the two assays detect two functionally distinct T cell populations and that the effector cells are not assayed by the 51Cr-release assay. Furthermore, the combination of cell depletion and enzyme-linked immunospot analyses showed that the effector cells were confined into a CD8+ CD45RO+ CD28- population. The persistence of effector CD8+ T cells specific for both the structural and nonstructural viral proteins in uninfected HCV-HFM, suggest that: 1) an immunological memory is established upon a subclinical infection without any evidence of hepatitis, in a large cohort of HCV-exposed individuals; 2) because these cells required neither restimulation nor the addition of particular cytokines in vitro for differentiating in effectors, they should be capable of prompt HCV-specific effector function in vivo, possibly providing antiviral protection; and 3) the maintenance of effector T cell responses may be sustained by persisting low-level stimulation induced by inapparent infections.

Original languageEnglish
Pages (from-to)6681-6689
Number of pages9
JournalJournal of Immunology
Volume162
Issue number11
Publication statusPublished - Jun 1 1999

ASJC Scopus subject areas

  • Immunology

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    Scognamiglio, P., Accapezzato, D., Casciaro, M. A., Cacciani, A., Artini, M., Bruno, G., Chircu, M. L., Sidney, J., Southwood, S., Abrignani, S., Sette, A., & Barnaba, V. (1999). Presence of effector CD8+ T cells in hepatitis C virus-exposed healthy seronegative donors. Journal of Immunology, 162(11), 6681-6689.