This study documents the curing of a congenitally acquired chronic viral infection and the acquisition of T-cell competence by a previously tolerant host. Infection of mice with lymphocytic choriomeningitis virus (LCMV) is a classic model of viral persistence and antigen-specific T-cell unresponsiveness. Mice infected at birth or in utero become lifelong carriers with no detectable virus-specific cytotoxic T lymphocyte (CTL) responses. This chronic infection can be eliminated by adoptive transfer of Lyt-2+ T cells from LCMV-immune mice. To determine whether these cured carriers were capable of generating their own LCMV-specific CTL response, mice congenic at the Thy-1 locus (Thy-1.1 and Thy-1.2) were used in the adoptive transfer experiments. Host-derived T-cell responses were checked after treating the cured carriers with a monoclonal antibody to deplete the immune donor T cells. Such cured carrier mice were able to generate a host-derived virus-specific CTL response and resisted a second LCMV challenge in the absence of any donor T cells. In addition, bone marrow cells from these cured carriers could functionally reconstitute irradiated mice. Thus this report demonstrates the acquisition of LCMV-specific T-cell competence by previously unresponsive carrier mice infected in utero. These results show that exposure to a virus even during embryonic life does not cause a permanent deletion of specific T cells. These findings are of significance to the understanding of tolerance mechanisms and have implications for the treatment of chronic viral infections
To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.