T cell receptor variable β gene repertoire in liver and peripheral blood lymphocytes of chronically hepatitis C virus‐infected patients with and without mixed cryoglobulinaemia

Summary To characterize the repertoire of T lymphocytes in chronically hepatitis C virus ( HCV) ‐infected patients with and without mixed cryoglobulinaemia ( MC ). T cell receptor ( TCR ) variable ( V ) β clonalities in portal tracts isolated from liver biopsy sections with a laser capture microdissection technique in 30 HCV ‐positive MC patients were studied by size spectratyping. Complementarity‐determining region 3 ( CDR3 ) profiles of liver‐infiltrating lymphocytes ( LIL ) were also compared with those circulating in the blood. The representative results of TCR Vβ by CDR3 were also obtained from liver tissues and peripheral blood lymphocytes ( PBL ) of 21 chronically HCV ‐infected patients without MC . LIL were highly restricted, with evidence of TCR Vβ clonotypic expansions in 23 of 30 (77%) and in 15 of 21 (71%) MC and non‐ MC patients, respectively. The blood compartment contained TCR Vβ expanded clones in 19 (63%) MC and 12 (57%) non‐ MC patients. The occurrence of LIL clonalities was detected irrespective of the degree of liver damage or circulating viral load, whereas it correlated positively with higher levels of intrahepatic HCV RNA . These results support the notion that TCR Vβ repertoire is clonally expanded in HCV ‐related MC with features comparable to those found in chronically HCV ‐infected patients without MC .