The presence of GM-CSF and IL-4 interferes with effect of TGF-beta1 on antigen presenting cells in patients with multiple sclerosis and in rats with experimental autoimmune encephalomyelitis.
The possibility to generate and expand tolerogenic dendritic cells (DC) with TGF-beta1 in vitro opens new therapeutic perspectives for the treatment of autoimmune diseases. In the present study, GM-CSF+IL-4 induced the differentiation of DC from adherent peripheral blood mononuclear cells, which had a higher expression of HLA-DR, CD86 and CD1a and the capacity to stimulate T cells. TGF-beta1 alone slightly promoted the generation of antigen presenting cells (APC) with higher expression of CD14, but did not differentiate them into E-cadherin+Langerhans cell (LC)-like DC. TGF-beta1-driven APC exhibited the morphology, phenotypes and functions of tolerogenic immature DC, and had lower capacity to stimulate T cells. In vivo experiment demonstrates that TGF-beta1-treated APC exhibited the therapeutic potential in Lewis rats with experimental autoimmune encephalomyelitis (EAE), followed by increase of IL-10 production in lymph nodes and decrease of inflammatory cells in spinal cords. Most importantly, GM-CSF/IL-4 used in DC preparation abolished the effect of TGF-beta1 to induce tolerogenic APC in vitro and in vivo. The results reveal that the usage of GM-CSF for the generation of tolerogenic DC should not be copied from DC preparation for anti-tumor therapy.
Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China. bgxiao@shmu.edu.cn
Bao-Guo
BG
Xiao
Wen-Hua
WH
Zhu
Chuan-Zhen
CZ
Lu
D000328:Adult; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology*; D007963:Leukocytes, Mononuclear; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000276:immunology* / Q000627:therapeutic use
D015820:Cadherins; D018950:Lipopolysaccharide Receptors; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor