The occurrence of chronic tick-borne encephalitis viral antigenemia characterized by the asymptomatic course or minimal clinical manifestations is caused by the virus-immune cell interaction. Cellular immunity was studied in 183 patients with chronic (more than 6-month) tick-borne encephalitis viral antigenemia, by evaluating the immunophenotypic and cytogenetic statuses, structural and functional features, cytokine profile, and peripheral lymphocytic apoptosis. The findings suggest impairments in the cooperation of immunocompetent cells and in the classical scheme of antiviral immunity regulation in tick-borne encephalitis viral persistence due to the changes in lymphocytic structural and functional properties.