Immunological tolerance to lymphocytic choriomeningitis virus in neonatally infected virus carrier mice: evidence supporting a clonal inactivation mechanism

Abstract

Previous studies have shown that no cell-mediated immunity against LCM virus-infected cells can be detected in neonatally established LCM virus carrier mice suggesting that they are immunologically tolerant to virally-altered cell membrane antigens. In this communication experiments are described aimed at analyzing the mechanism. Virus-specific cell-mediated immunity was assessed by 51Cr release and target cell reduction assays. Attempts to demonstrate cells in spleens of CBA/J carrier mice able to suppress in syngeneic recipients the induction or the effector phase of the cytotoxic T-cell response against LCM virus-infected cells were unsuccessful. Also, no factors were detected in CBA/J and C57BL/6J carrier mice, either spleen cell-associated or free in the circulation, which would block the activity of cytotoxic T-lymphocytes against LCM virus-infected syngeneic target cells. The results indicate that inability of LCM virus carrier mice to act immunologically against virus-infected target cells is due to deletion or irreversible inactivation of T lymphocytes carrying receptors for virally altered cell membrane antigens.