Differential expansion of T-cell receptor variable beta subsets after antigenic stimulation in patients with different outcomes of hepatitis C infection

Persistent antigenic stimulation during chronic hepatitis C may alter the T-cell receptor variable chain beta (TCR BV) repertoire as well as the cytokine responses of hepatitis C virus (HCV)-specific T lymphocytes. We analysed the distribution of the TCR BV subsets 2.1, 3.1, 5.1, 6.1, 8, 13.1, 13.6, 14.1, 17.1, 21.3 in relation to intracytoplasmic expression of interleukin-2, interferon-gamma, interleukin-4 and interleukin-10. Using flow cytometry, CD45RO(+) memory T cells of 27 patients with chronic hepatitis C, eight patients with resolved HCV infection and 16 non-HCV-related controls were studied with and without stimulation by the HCV core, NS3, NS4, NS5a and NS5b proteins. Patients with chronic and resolved hepatitis C differed by larger basal TCR BV2.1(+) , BV6.1(+) , BV17.1(+) and BV21.3(+) subsets in chronic hepatitis C, which were correlated to the numbers of T cells with spontaneous interleukin-2 and interferon-gamma production (r =0.51-0.73, P <0.05). Upon HCV-specific stimulation these subsets did not expand, whereas a marked in vitro expansion of TCR BV8(+) T cells in response to all HCV proteins was selectively noted in chronic hepatitis C (P <0.05). This expansion of TCR BV8(+) memory T cells was significantly correlated to HCV-induced interleukin-10 expression (r =0.58-0.98, P <0.01). Thus, differential involvement of selected TCR BV subsets may be related to the outcome of HCV infection.