In vivo state of antiviral CTL precursors. Characterization of a cycling cell population containing CTL precursors in immune mice.
The in vivo state of CD8+ mouse memory CTL specific to lymphocytic choriomeningitis virus (LCMV) was characterized. During acute LCMV infection, the majority of the LCMV-specific CTL activity tested immediately ex vivo was mediated by CD8+ L-selectin- Mac-1+ CTL. The L-selectin- population of CD8+ cells elicited during acute infection also carried > 99% of the restimulatable CD8+ CTL precursors (CTLp) to LCMV, and these required added IL-2 for development into effectors in vitro. In contrast with the acute infection, most of the virus-specific CTLp in immune mice were L-selectin+. Examination of CD8+ T cells in LCMV-immune mice revealed that a L-selectin+ blast-size population of cycling CD8+ cells contained CTLp, which developed into effector CTL in the absence of added IL-2. These cells also expressed Mac-1 and IL-2R. Flow cytometric sorting for IL-2R+ and IL-2R- CD8+ cells in the immune animal revealed, by limiting dilution analysis, similar frequencies of CTLp in both populations. In bulk restimulation assays, the CD25+ CTLp did not require added IL-2 for their in vitro development into effectors, whereas the CD25- CTLp did. Hence, the different requirements for CTLp to effector development in vitro reflect qualitative differences in the in vivo state of the CTLp in the various subpopulations. LCMV-specific memory CTLp that did not require added IL-2 for differentiation were also found in the small-size, noncycling, CD8+L-selectin- cells. In contrast, the small-size, noncycling, CD8+L-selectin+, and CD8+IL-2R- populations also carried CTLp, but these required added IL-2 for development into effector CTL. Hence, T cell memory to LCMV is distributed among various lymphocyte subpopulations in immune animals, and the presence of an activated cycling cell component may account for the long-term perpetuation of antiviral immunologic memory.
Razvi
E S
ES
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655.
Welsh
R M
RM
McFarland
H I
HI
D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002453:Cell Cycle / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D016130:Immunophenotyping; D019041:L-Selectin; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D016177:Macrophage-1 Antigen; D015375:Receptors, Interleukin-2; D019041:L-Selectin