T cell memory. Long-term persistence of virus-specific cytotoxic T cells.
This study documents that virus-specific CTL can persist indefinitely in vivo. This was accomplished by transferring Thy-1.1 T cells into Thy-1.2 recipient mice to specifically identify the donor T cell population and to characterize its antigenic specificity and function by using a virus-specific CTL assay. Thy-1.1+ T cells from mice previously immunized with lymphocytic choriomeningitis virus (LCMV) were transferred into Thy-1.2 mice persistently infected with LCMV. The transferred LCMV-specific CTL (Thy-1.1+ CD8+) eliminate virus from the chronically infected carriers and persist in the recipient mice in small numbers, comprising only a minor fraction of the total T cells. Upon re-exposure to virus, these long-lived "resting" CD8+ T cells proliferate in vivo to become the predominant cell population. These donor CD8+ T cells can be recovered up to a year post-transfer and still retain antigenic specificity and biological function. They kill LCMV infected H-2-matched cells in vitro and can eliminate virus upon transfer into a second infected host. In addition, these long-lived CD8+ T cells appear not to be dependent on help from CD4+ T cells, since depletion of CD4+ T cells has minimal or no effect on their biological properties (proliferation, CTL response, viral clearance). These donor CTL also exhibit an immunodominance over the host-derived LCMV-specific CTL response. When both host and donor T cells are present, the donor CTL response is dominant over the potential CTL response of the cured carrier host. Taken together, these results suggest that virus-specific CTL can persist for the life span of the host as memory cells.
Jamieson
B D
BD
Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, CA 90024.
Ahmed
R
R
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral / Q000276:immunology*; D016827:CD8 Antigens; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D007116:Immunization, Passive; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000382:microbiology; D008217:Lymphocytic choriomeningitis virus / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology* / Q000637:transplantation
D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D016827:CD8 Antigens; D000939:Epitopes