Long-term effects of IFN-gamma, IL-10, and TGF-beta-modulated dendritic cells on immune response in Lewis rats.
Increasing data have shown that IFN-gamma, IL-10, and TGF-beta-modulated dendritic cells (DC) provide a promising strategy in treatment of experimental allergic encephalomyelitis and experimental autoimmune myasthenia gravis through different manner. To explore the immune response status after long-term application of these cytokine-modulated-DC, Lewis rats were injected subcutaneously into naive DC and IFN-gamma, IL-10, and TGF-beta-modulated DC (i.e., IFN-gamma-DC, IL-10-DC, and TGF-beta-DC) at does of 1 x 10(6) cells/rat every month for continuous 18 months, respectively. No rats suffered from decreased vigor and activity as well as cachectic condition during 18-month observation, and no rats had body-weight loss after 18-month treatment. Exploratory laparectomy did not find any tumor in all rats. IL-10-DC and TGF-beta-DC resulted in lower nonspecific (Con A-induced) and antigen specific (ovalbumin-stimulated) spleen mononuclear cells proliferation, accompanied by lower levels of IFN-gamma, IL-10, and TNF-alpha. On the contrary, IFN-gamma-DC did not suppress cell proliferation and IFN-gamma and IL-10 production except only slightly decreased TNF-alpha levels. These results suggest that IFN-gamma-DC seems to be a more ideal candidate in the treatment of autoimmune diseases without suppressing immune response.
Duan
Rui-Sheng
RS
Division of Neuroimmunology Neurotec, Karolinska Institute, Stockholm, Sweden.
Link
Hans
H
Xiao
Bao-Guo
BG
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000494:pharmacology*; D016753:Interleukin-10 / Q000032:analysis / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
Immunol Cell Biol. 2000 Apr;78(2):161-5
10762417
Int Immunol. 2004 Jan;16(1):13-22
14688056
Int Immunol. 2002 Jan;14(1):65-8
11751753
BioDrugs. 2003;17(2):103-11
12641489
Semin Oncol. 2003 Jun;30(3 Suppl 8):23-9
12881809
Immunol Rev. 2001 Dec;184:117-28
11918681
Annu Rev Immunol. 1991;9:271-96
1910679
Clin Exp Immunol. 2002 Feb;127(2):214-9
11876742
Clin Exp Immunol. 1999 Jul;117(1):38-43
10403913
J Immunol. 1997 Nov 15;159(10):4772-80
9366401
Nat Immunol. 2001 Jul;2(7):585-9
11429541
Neurobiol Dis. 2004 Jul;16(2):461-7
15193302
J Immunol. 2000 Aug 1;165(3):1175-81
10903714