Cytokine production by mouse myeloid dendritic cells in relation to differentiation and terminal maturation induced by lipopolysaccharide or CD40 ligation

被引:193
作者
Morelli, AE
Zahorchak, AF
Larregina, AT
Colvin, BL
Logar, AJ
Takayama, T
Falo, LD
Thomson, AW
机构
[1] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Med Ctr, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Med Ctr, Dept Dermatol, Pittsburgh, PA 15213 USA
[4] Univ Pittsburgh, Med Ctr, Inst Canc, Pittsburgh, PA 15213 USA
[5] Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15213 USA
关键词
D O I
10.1182/blood.V98.5.1512
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Although it is known that dendritic cells (DCs) produce cytokines, there is little Information about how cytokine synthesis is regulated during DC development. A range of cytokine mRNA/proteins was analyzed in Immature (CD86(-)) or mature (CD86(+)) murine bone marrow (BM)derived DCs. Highly purified, flow-sorted, immature DCs exhibited higher amounts of interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor beta1 (TGF-beta1), and macrophage migration inhibitory factor (MIF) mRNA/protein than mature DCs. After differentiation, DC up-regulated the levels of IL-6 and IL-15 mRNA/protein and synthesized de novo, mRNA/protein for IL-12p35, IL-12p40, and IL-18. Although immature BM-derived DCs did not stimulate naive allogeneic T cells, mature DCs elicited a mixed population of T helper (Th) 1 (mainly) and Th2 cells in 3d-mixed leukocyte reactions. CD86+ BM DCs switched to different cytokine patterns according to whether they were terminally differentiated by lipopolysaccharide (LIPS) or CD40 ligation. Although both stimuli increased IL-6, IL-12p40, IL-15, and TNF-alpha mRNA/protein levels, only LPS up-regulated transcription of IL-1 alpha, IL-1 beta, IL-12p35, and MIF genes. Although LPS and CD40 crosslinking increased the T-cell allostimulatory function of BM DCs, only LIPS stimulation shifted the balance of naive Th differentiation to Th1 cells, a mechanism dependent on the up-regulation of IL-12p35 and not of IL-23. These results demonstrate that, depending on the stimuli used to terminally mature BM DCs, DCs synthesize a different pattern of cytokines and exhibit distinct Th cell-driving potential. (C) 2001 by The American Society of Hematology.
引用
收藏
页码:1512 / 1523
页数:12
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