Presence of effector CD8+ T cells in hepatitis C virus-exposed healthy seronegative donors.
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 severalfold 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.
Scognamiglio
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Fondazione Andrea Cesalpino, Istituto di I Clinica Medica and Dipartimento di Malattie Infettive, Università di Roma La Sapienza, Italy.
Accapezzato
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D
Casciaro
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MA
Cacciani
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Artini
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Bruno
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Chircu
M L
ML
Sidney
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Southwood
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Abrignani
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Sette
A
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Barnaba
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V
D000293:Adolescent; D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D018106:CD28 Antigens / Q000032:analysis; D002460:Cell Line; D002469:Cell Separation; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood*; D018936:Hepatitis C Antigens / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D013234:Stem Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D009842:Oligopeptides; D017493:Leukocyte Common Antigens