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

CTL responses against multiple hepatitis C virus (HCV) epitopes were detect ed in 7 of 29 (24.1%) healthy family members (HFM) persistently exposed to chronically HCV-infected patients (HCV-HFM). These precursor CTL were at ve ry low or undetectable frequencies, as determined by limiting dilution anal ysis, 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 C TL, These results indicate that the two assays detect two functionally dist inct T cell populations and that the effector cells are not assayed by the Cr-51-release assay. Furthermore, the combination of cell depletion and enz yme-linked immunospot analyses showed that the effector cells were confined into a CD8(+) CD45RO(+) CD28(-) population. The persistence of effector CD 8(+) T cells specific for both the structural and nonstructural viral prote ins in uninfected HCV-HFM, suggest that: 1) an immunological memory is esta blished 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 effecters, they should be capable of prompt HCV-specifi c effector function in vivo, possibly providing antiviral protection; and 3 ) the maintenance of effector T cell responses may be sustained by persisti ng low-level stimulation induced by inapparent infections.