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

Prahlad Parajuli, R. Lee Mosley, Vladimir Pisarev, Jennifer Chavez, Amy Ulrich, Michelle Varney, Rakesh K. Singh, James E. Talmadge

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Objective: Mechanisms of T-cell stimulation by Flt3 ligand (Flt3L) and granulocyte-macrophage colony-stimulating factor (GM-CSF) remain unclear. Herein, we compared the effects of Flt3L and GM-CSF on the expansion of dendritic cells (DC) and T-cell subsets and cytokine expression. Methods: Naïve and effector/memory T cells were analyzed by flow cytometry (FC). CD4+ and CD8+ T cells and CD11c+CD11bdull/- (DC1) and CD11c+CD11b+ (DC2) subsets were isolated and the frequency of IFN-γ-, IL-12- (type 1) and IL-4-, IL-10 (type 2)-producing cells and cytokine mRNA expression evaluated. Results: Flt3L expanded both DC1 and DC2 subsets with a significantly higher percentage and number of DC1 than DC2, while GM-CSF preferentially expanded 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 DC2. The numbers of naïve and memory T cells were elevated in mice that received Flt3L or GM-CSF. However, the number of memory CD4+ and CD8+ T cells was significantly increased in Flt3L as compared to GM-CSF cohorts. While GM-CSF increased the frequency of both type 1 and type 2 cytokine-producing cells, Flt3L significantly augmented the frequency of type 1 T cells. Conclusions: In contrast to GM-CSF, Flt3L preferentially induces the expansion 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.

Original languageEnglish (US)
Pages (from-to)1185-1193
Number of pages9
JournalExperimental Hematology
Volume29
Issue number10
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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