scholarly journals Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 5875-5884 ◽  
Author(s):  
Hideaki Tanizaki ◽  
Gyohei Egawa ◽  
Kayo Inaba ◽  
Tetsuya Honda ◽  
Saeko Nakajima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Actin Polymerization ◽  
Cell Stimulation ◽  
T Cell Stimulation ◽  
Acquired Immune Responses

Abstract Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1−/−) mice, adhesion and spreading to cellular matrix were impaired in mDia1−/− bone marrow–derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1−/− DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.

The role of N-linked oligosaccharides of MHC class II antigens in T cell stimulation

1994 ◽  
Vol 172 (1) ◽  
pp. 95-104 ◽  
Author(s):  
Bishwajit Nag ◽  
H. Garrett Wada ◽  
Subhashini Arimilli ◽  
Katherine Fok ◽  
David Passmore ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cell Stimulation ◽  
T Cell Stimulation ◽  
Mhc Class Ii Antigens ◽  
Class Ii Antigens

Reduction of Factor VIII Inhibitor Formation with F.VIII-Pulsed Tolerogenic Dendritic Cells in the Murine Hemophilia A Model.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 213-213 ◽  
Author(s):  
Margaret V. Ragni ◽  
Wenhu Wu ◽  
Xiaoyan Liang ◽  
Lina Lu
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
T Cell ◽  
Hemophilia A ◽  
Binding Activity ◽  
Control Group ◽  
High Morbidity ◽  
Gm Csf

Abstract Inhibitor formation is a severe complication of hemophilia, occurring in up to 25% and associated with poor response to factor replacement, uncontrolled bleeding, and high morbidity. Preventing inhibitor formation is, thus, a major goal of hemophilia management. The role of dendritic cells (DC) in regulating immune response has been increasingly recognized: immature DC (imDC) induce T regulatory cells in vitro and promote Ag-specific tolerance in vivo. We, therefore, studied the role of imDC propagated from bone marrow with GM-CSF + TGFβ to prevent inhibitor formation in the hemophilia A murine model. Following tail vein injection of recombinant F.VIII (Advate, Baxter) 2.5 U (0.2 μg) on days 0, 2, and 4 in hemophilia A exon 16 KO C57Bl/6 mice, anti-VIII antibodies were detected by semi-quantitative APTT (scored 1-4), peaking on day 6. On rechallenge with F.VIII 2.5 U on days 12, 14, and 16, anti-VIII was detected, peaking on day 17. Anti-VIII production was associated with high level splenic T cell proliferation in response to F.VIII stimulation in vitro, measured by 3H-thymidine incorporation in mixed lymphocyte reaction (MLR). By contrast, there was no antibody formation in F.VIII-treated Wt C57Bl/6 mice: the latter was associated with low T cell response to F.VIII in vitro. Functionally immature DC (imDC) were propagated from the bone marrow of hemophilia A mice with GM-CSF (4ng/ml) and TGFβ (0.2ng/ml). For comparison, functionally mature dendritic cells (mDC) were propagated with GM-CSF (4ng/ml) and IL-4 (1000U/ml).The former (imDC) demonstrated deficient NF-kB binding activity in nuclear protein as detected by gel shifting assay and expressed low level of costimulatory molecules CD80, CD86; by contrast, the latter (mDC) demonstrated enhanced NF-kB binding activity and high levels of co-stimulatory molecules. Administration of 2x106 F.VIII-pulsed imDC (20U/ml x 24h) 7 days before F.VIII dosing on days 0, 2, and 4, led to reduction in inhibitor formation on day 6 (score 1.6 vs. 2.3 in control group) which was further reduced on day 8 (score 1.0 vs. 2.0 in control group). The inhibitor could not be detected on day 8 in 2 of 4 mice pretreated with F.VIII-pulsed imDC. By contrast, high levels of inhibitor were detected in mice pretreated with F.VIII-pulsed mDC (score 3.3). Rechallenge with F.VIII on day 10 in imDC-treated mice resulted in no increase in the reduced or absent anti-VIII effect on day 12. Splenic T cells (CD3+) from the imDC-pretreated mice showed lower proliferative capacity when restimulated in vitro with F.VIII, suggesting that imDC induced F.VIII unresponsiveness. These studies show that FVIII-pulsed imDC reduce the intensity of inhibitor formation, and suggest the potential role of modified DC in preventing or reducing F.VIII inhibitor formation.

scholarly journals CD83 Knockdown in Monocyte-Derived Dendritic Cells by Small Interfering RNA Leads to a Diminished T Cell Stimulation

2007 ◽  
Vol 178 (9) ◽  
pp. 5454-5464 ◽  
Author(s):  
Alexander T. Prechtel ◽  
Nadine M. Turza ◽  
Alexandros A. Theodoridis ◽  
Alexander Steinkasserer
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Small Interfering Rna ◽  
Cell Stimulation ◽  
T Cell Stimulation ◽  
Interfering Rna

Dendritic cells fused with human cancer cells: morphology, antigen expression, and T cell stimulation

2004 ◽  
Vol 113 (3) ◽  
pp. 261-269 ◽  
Author(s):  
Shigeo Koido ◽  
Masaya Ohana ◽  
Chunlei Liu ◽  
Najmosama Nikrui ◽  
John Durfee ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Human Cancer ◽  
Antigen Expression ◽  
Cell Stimulation ◽  
Human Cancer Cells ◽  
T Cell Stimulation
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