Polarization of naive T cells into Th1 or Th2 by distinct cytokine-driven murine dendritic cell populations: implications for immunotherapy

Abstract

Dendritic cells (DCs) activate T cells and regulate their differentiation into T helper cell type 1 (Th1) and/or Th2 cells. To identify DCs with differing abilities to direct Th1/Th2 cell differentiation, we cultured mouse bone marrow progenitors in granulocyte macrophage-colony stimulating factor (GM), GM + interleukin (IL)-4, or GM + IL-15 and generated three distinct DC populations. The GM + IL-4 DCs expressed high levels of CD80/CD86 and major histocompatibility complex (MHC) class II and produced low levels of IL-12p70. GM and GM + IL-15 DCs expressed low levels of CD80/CD86 and MHC class II. The GM + IL-15 DCs produced high levels of IL-12p70 and interferon (IFN)-gamma, whereas GM DCs produced only high levels of IL-12p70. Naive T cells stimulated with GM + IL-4 DCs secreted high levels of IL-4 and IL-5 in addition to IFN-gamma. In contrast, the GM + IL-15 DCs induced higher IFN-gamma production by T cells with little or no Th2 cytokines. GM DCs did not induce T cell polarization, despite producing large amounts of IL-12p70 following activation. A similar pattern of T cell activation was observed after in vivo administration of DCs. These data suggest that IL-12p70 production alone, although necessary for Th1 differentiation, is not sufficient to induce Th1 responses. These studies have implications for the use of DC-based vaccines in immunotherapy of cancer and other clinical conditions.

Lack of IL-15 results in the suboptimal priming of CD4+T cell response against an intracellular parasite

“…Our studies demonstrate that DCs from mice lacking IL-15 exhibit decreased IL-12 response to Toxoplasma stimulation and are less effective in priming of CD4 ϩ T cells, which in turn leads to lower inflammatory response in the infected animal. These findings are supported by recent observations demonstrating that priming with IL-15-treated DCs can strongly polarize CD4 ϩ T cells toward production of IFN-␥ (28). Although the knockout animals have a higher parasite load in comparison with WT mice, especially in the gut, they survive the infection because of milder pathology in the tissue.…”

“…In normal immunocompetent mice, T. gondii infection induces a rapid and large IL-12 production by DCs (14). Moreover, recent studies have demonstrated that IL-15 treatment of DCs results in higher IL-12 production by these cells (28). To establish that DCs from knockout mice are hypo-responsive to T. gondii infection, the level of IL-12 production by DCs from IL-15 knockout mice was evaluated.…”

“…Next, we determined whether downregulated CD4 ϩ T cell immunity in IL-15 Ϫ/Ϫ mice was due to inadequate priming of this T cell subset. Because dendritic cells (DCs) are known to play a key role in the initiation of immune response (28,29), we evaluated CD4 ϩ T cells priming against TLA by DCs from IL-15 Ϫ/Ϫ and parental WT mice. DCs from MLN of naïve WT or knockout animals were isolated and pulsed with TLA in an overnight culture.…”

The Pseudomonas aeruginosa Mannose Sensitive Hamemagglutination Strain (PA-MSHA) Induces a Th1-Polarizing Phenotype by Promoting Human Dendritic Cells Maturation

“…Dentritic Cells influence Th cells proliferation, which most commonly polarize to Th1 or Th2 cells [19]. IL-12 excreted by DCs stimulates the secretion of IFN-c by Th cells [20].…”

Avaliação do papel da nattectina, toxina do veneno de Thalassophryne nattereri, na respota imune inata e específica.

“…Recentemente foi isolada uma lectina tipo C da moréia Conger myriaster importante na resposta imune inata, (GALLIN et al, 1988PAUL, 1998 de proliferação e diferenciação em célula efetora Th1 ou Th2. Vários estudos sugerem que os níveis de moléculas co-estimulatórias expressas nas células dendríticas e as citocinas presentes no micro-ambiente durante a ativação da célula T são importantes para a sua ativação (FEILI-HARIRI et al, 2005).…”