Flt3 ligand and granulocyte-macrophage colony-stimulating factor preferentially expand and stimulate, different dendritic and T-cell subsets

Objective. Mechanisms of T-cell stimulation by Flt3 ligand (Flt3L) and gran ulocyte-macrophage colony-stimulating factor (GM-CSF) remain unclear. Herei n, we compared the effects of Flt3L and GM-CSF on the expansion of dendriti c cells (DC) and T-cell subsets and cytokine expression. Methods. Naive and effector/memory T cells were analyzed by flow cytometry (FC). CD4(+) and CD8(+) T cells and CD11c(+)CD11(dull/-)(DC1) and CD11c(+)C D11b(+) (DC2) subsets were isolated and the frequency of IFN-gamma-, IL-12- (type 1) and IL-4-, IL-10 (type 2)-producing cells and cytokine mRNA expre ssion evaluated. Results. Flt3L expanded both DC1 and DC2 subsets with a significantly highe r percentage and number of DC1 than DC2, while GM-CSF preferentially expand ed the DC2 subset. Isolated DC1 from Flt3L-injected mice had significantly higher levels of IL-12 (p40) than IL-10, while the converse occurred with D C2. The numbers of naive and memory T cells were elevated in mice that rece ived Flt3L or GM-CSF. However, the number of memory CD4(+) and CD8(+) T cel ls was significantly increased in Flt3L as compared to GM-CSF cohorts. Whil e GM-CSF increased the frequency of both type 1 and type 2 cytokine-produci ng cells, Flt3L significantly augmented the frequency of type 1 T cells. Conclusions. In contrast to GM-CSF, FIt3L preferentially induces the expans ion of type 1 T cells. The mechanism of Flt3L-induced T-cell stimulation is associated with the expansion of the IL-12 (p40)-producing DC1 and memory T cells. (C) 2001 International Society for Experimental Hematology. Publis hed by Elsevier Science Inc.