T-cell tolerance: exposure to virus in utero does not cause a permanent deletion of specific T cells.
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.
Jamieson
B D
BD
Department of Microbiology and Immunology, University of California, Los Angeles School of Medicine 90024.
Ahmed
R
R
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D002353:Carrier State / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D007108:Immune Tolerance; D007116:Immunization, Passive; D007121:Immunocompetence; D007153:Immunologic Deficiency Syndromes / Q000209:etiology*; D008216:Lymphocytic Choriomeningitis / Q000151:congenital / Q000276:immunology* / Q000628:therapy; D008217:Lymphocytic choriomeningitis virus / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C / Q000196:embryology / Q000276:immunology; D008810:Mice, Inbred C57BL / Q000196:embryology / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation