Distinct patterns of T cell receptor distribution of peripheral blood CD8+ cells during different stages of chronic infection with hepatitis B virus.

We compared the Vbeta TCR repertoires of CD8+ peripheral blood lymphocytes between 21 patients with chronic hepatitis B (CHB) and 9 healthy individuals, using RT-PCR analysis. Several differences were seen between CHB patients and controls, including a marked increase in the expression of two to five Vbeta families in the CHB patients. There was no evidence for a superantigen effect, although an increase in Vbeta7 was seen in 64% of patients. A significant under-expression of Vbeta families were also detected, particularly in patients with active liver disease in which under-expression of Vbeta14 and Vbeta15 was associated with acute exacerbations of liver disease. We also did a longitudinal analysis of the TCR repertoire in two patients over a period of 6 months, from the initiation of a disease flare to its resolution. One patient continued to experience spontaneous flares following the completion of this study, while the other patient underwent spontaneous remission with long-term (> 12 months) loss of HBeAg following resolution of the flare. The TCR repertoires of both patients were altered during the flare, and there was a higher degree of TCR variability in the patient who went into remission.