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 c horiomeningitis virus (LCMV) was characterized. During acute LCMV infe ction, the majority of the LCMV-specific CTL activity tested immediate ly ex vivo was mediated by CD8(+) L-selectin(-) Mac-1(+) CTL. The L-se lectin(-) population of CD8(+) cells elicited during acute infection a lso carried >99% of the restimulatable CD8(+) CTL precursors (CTLp) to LCMV, and these required added IL-2 for development into effecters in vitro. In contrast with the acute infection, most of the virus-specif ic CTLp in immune mice were L-selectin(+). Examination of CD8(+) T cel ls in LCMV-immune mice revealed that a L-selectin(+) blast-size popula tion of cycling CD8(+) cells contained CTLp, which developed into effe ctor 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, si milar frequencies of CTLp in both populations. In bulk restimulation a ssays, the CD25(+) CTLp did not require added IL-2 for their in vitro development into effecters, whereas the CD25(-) CTLp did. Hence, the d ifferent requirements for CTLp to effector development in vitro reflec t qualitative differences in the in vivo state of the CTLp in the vari ous subpopulations. LCMV-specific memory CTLp that did not require add ed IL-2 for differentiation were also found in the small-size, noncycl ing, CD8(+)L-selectin(-) cells. In contrast, the small-size, noncyclin g, CD8(+)L-selectin(+), and CD8(+)IL-2R(-) populations also carried CT Lp, but these required added IL-2 for development into effector CTL. H ence, T cell memory to LCMV is distributed among various lymphocyte su bpopulations in immune animals, and the presence of an activated cycli ng cell component may account for the long-term perpetuation of antivi ral immunologic memory.