title: High frequencies of virus-specific CD8+ T-cell precursors.
abstract: A productive CD8(+) T-cell response to a viral infection requires rapid division and proliferation of virus-specific CD8(+) T cells. Tetramer-based enrichment assays have recently given estimates of the numbers of peptide-major histocompatibility complex-specific CD8(+) T cells in naïve mice, but precursor frequencies for entire viruses have been examined only by using in vitro limiting-dilution assays (LDAs). To examine CD8(+) T-cell precursor frequencies for whole viruses, we developed an in vivo LDA and found frequencies of naïve CD8(+) T-cell precursors of 1 in 1,444 for vaccinia virus (VV) ( approximately 13,850 VV-specific CD8(+) T cells per mouse) and 1 in 2,958 for lymphocytic choriomeningitis virus (LCMV) ( approximately 6,761 LCMV-specific CD8(+) T cells per mouse) in C57BL/6J mice. In mice immune to VV, the number of VV-specific precursors, not surprisingly, dramatically increased to 1 in 13 ( approximately 1,538,462 VV-specific CD8(+) T cells per mouse), consistent with estimates of VV-specific memory T cells. In contrast, precursor numbers for LCMV did not increase in VV-immune mice (1 in 4,562, with approximately 4,384 LCMV-specific CD8(+) T cells per VV-immune mouse). Using H-2D(b)-restricted LCMV GP33-specific P14-transgenic T cells, we found that, after donor T-cell take was accounted for, approximately every T cell transferred underwent a full proliferative expansion in response to LCMV infection. This high efficiency was also seen with memory populations, suggesting that most antigen-specific T cells will proliferate extensively at a limiting dilution in response to infections. These results show that frequencies of naïve and memory CD8(+) T cell precursors for whole viruses can be remarkably high.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Mina O
authors.initials: MO
authors.lastname: Seedhom
authors.forename: Evan R
authors.initials: ER
authors.lastname: Jellison
authors.forename: Keith A
authors.initials: KA
authors.lastname: Daniels
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Welsh
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*