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M Feili-Hariri

Publications and source records attributed to M Feili-Hariri.

9 recordsLinked to original sources
PubMed2004

Qualitative and quantitative abnormalities in splenic dendritic cell populations in NOD mice.

The phenotype and function of splenic DC populations from diabetes-prone NOD mice were characterized and compared to DC from diabetes-resistant strains in the presence or absence of Flt3 ligand (FL) treatment. NOD mice were found to have significantly fewer CD8alpha+ DC than both B10.BR and C57BL/6 mice, and this defect was reversed by FL treatment. Freshly isolated CD8alpha+ and CD8alpha- DC from all three strains were found to express similar levels of costimulatory molecules and this was similar in both FL-treated and untreated animals. IL-12 p40 production was significantly lower in purified CD11c+ DC from NOD mice compared to DC from C57BL/6 or B10.BR mice. CD8alpha+ DC isolated from NOD mice produced lower levels of IL-12p40 than CD8alpha+ DC from C57CBL/6 and this was dependent on the nature of the stimulus given. In contrast both CD8alpha+ and CD8alpha- DC from FL-treated mice produced high levels of IL-12p40 following activation, but only the CD8alpha- DC produced IL-12p70. Functionally, freshly isolated CD8alpha- DC were more stimulatory than CD8alpha+ DC in a primary allogeneic mixed lymphocyte reaction. However, DC maturation resulted in increased T cell stimulatory capacity for both DC subsets, and this pattern was seen in all strains. These results demonstrate significant differences in phenotype and function of splenic NOD CD8alpha+ DC, and further suggest that FL treatment may reverse some of these abnormalities.

Adjuvants, Immunologic↗
PubMed2003

Receptor-mediated endocytosis of iron-oxide particles provides efficient labeling of dendritic cells for in vivo MR imaging.

Dendritic cells (DCs) function as antigen presenting cells in vivo and play a fundamental role in numerous diseases. New methods are described for high-efficiency intracellular labeling of DCs with superparamagnetic iron-oxide (SPIO) utilizing a receptor-mediated endocytosis (RME) mechanism. Bone marrow-derived DCs or a fetal skin-derived DC line were incubated with SPIO conjugated to anti-CD11c monoclonal antibody (mAb) under conditions favoring RME. These cells exhibited approximately a 50-fold increase in uptake relative to DCs incubated with SPIO without the mAb. Flow cytometry studies assaying cell surface markers showed a down-modulation of CD11c, but no other changes in phenotype. Immunological function of the DCs was unmodified by the labeling, as determined by cytokine secretion assays. The RME mechanism was confirmed using electron microscopy, endocytosis inhibition assays, and incubation experiments with SPIO conjugated to mAbs against accessory molecules that are not expressed on DCs. Labeled DCs were injected into murine quadriceps and monitored in vivo for several days using MR microimaging at 11.7 T. DCs were observed to remain within the muscle for >24 hr. The use of RME is an efficient way to label immune cells for in vivo MRI and can be applied to a wide variety of cell types.

Animals↗
PubMed2003

Dendritic cells, T cell tolerance and therapy of adverse immune reactions.

Dendritic cells (DC) are uniquely able to either induce immune responses or to maintain the state of self tolerance. Recent evidence has shown that the ability of DC to induce tolerance in the steady state is critical to the prevention of the autoimmune response. Likewise, DC have been shown to induce several type of regulatory T cells including Th2, Tr1, Ts and NKT cells, depending on the maturation state of the DC and the local microenvironment. DC have been shown to have therapeutic value in models of allograft rejection and autoimmunity, although no success has been reported in allergy. Several strategies, including the use of specific DC subsets, genetic modification of DC and the use of DC at various maturation stages for the treatment of allograft rejection and autoimmune disease are discussed. The challenge for the future use of DC therapy in human disease is to identify the appropriate DC for the proposed therapy; a task made more daunting by the extreme plasticity of DC that has recently been demonstrated. However, the progress achieved to date suggests that these are not insurmountable obstacles and that DC may become a useful therapeutic tool in transplantation and autoimmune disease.

Animals↗
PubMed2001

Phenotypic and functional characteristics of BM-derived DC from NOD and non-diabetes-prone strains.

We compared BM-derived DC from NOD with DC from non-diabetes-prone strains. NOD myeloid progenitors cultured in GM or GM + IL-4 yielded lower numbers of DC than similar cultures from other strains. NOD GM + IL-4 DC produced lower amounts of IL-12 p70 following CD40 ligation or LPS stimulation in the presence of IFN-gamma than DC from other strains, although similar levels of IL-6 and NO were produced by all strains. The low amounts of IL-12 p70 produced by GM + IL-4 DC are despite a more mature DC phenotype observed in NOD mice. The low DC number could diminish the ability of DC to stimulate immunoregulatory T cells. Furthermore, the differentiation/maturation of DC from myeloid progenitors is altered, reflecting disorders in the function of these cells in NOD BM.

Animals↗
PubMed2000

Prevention of diabetes in the NOD mouse by a Th1 clone specific for a hsp60 peptide.

Peptide-based therapies have been shown to be effective in the prevention of diabetes in the NOD mouse. We have been interested in the T cell response elicited by such therapies and have been studying a T cell clone (C3.5) specific for hsp60 AA 437-460, generated following immunization with the hsp60 437-460 peptide. The C3.5 clone was CD4(+), Vbeta8.3 TCR(+), I-A(g7)restricted and of the Th1 type. The injection of this clone into prediabetic NOD mice prevented the adoptive transfer of the disease and suppressed the development of spontaneous diabetes. This effect was reflected in a reduction in the degree and severity of insulitis in mice injected with this clone. In addition, an antibody response was elicited to the C3.5 clone in mice given multiple injections of the clone. The epitope recognized by C3.5 is located in the N-terminus of the hsp60 AA 437-460 peptide, and this clone was unable to recognize the native hsp60 molecule. These data raise questions concerning the mechanism by which peptide-based therapies prevent autoimmune disease.

Adoptive Transfer↗
PubMed1999

Immunobiology of DC in NOD mice.

NOD mice spontaneously develop diabetes between 15 and 20 weeks of age, which is preceded by insulitis characterized by the infiltration of lymphocytes. Dendritic cells (DC) are among the first cells to infiltrate the islet and they have been implicated in the pathogenesis of the disease. Our work has been concerned with the detailed characterization of four distinct DC populations in NOD mice: two derived from bone marrow (BM) cells cultured in either granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4) or GM-CSF alone and two from the spleen of Flt3 ligand (Flt3L) -treated mice, isolated on the basis of CD8alpha expression. Phenotypic and functional differences between these DC subsets in NOD mice have been identified. In addition, we obtained a lower yield of NOD BM-derived DC and they expressed higher levels of cell-surface CD40 and IL-12 p40 mRNA than BM-derived DC from the diabetes-resistant strain, B10.BR. We have also investigated the ability of these DC populations to modulate the development and progression of diabetes in NOD mice.

Animals↗
PubMed1999

Immunotherapy of NOD mice with bone marrow-derived dendritic cells.

We evaluated two bone marrow-derived dendritic cell (DC) populations from NOD mice, the murine model for type 1 human diabetes. DCs derived from GM-CSF [granulocyte/macrophage colony-stimulating factor] + interleukin (IL)-4 cultures expressed high levels of major histocompatibility complex (MHC) class II, CD40, CD80, and CD86 molecules and were efficient stimulators of naive allogeneic T-cells. In contrast, DCs derived from GM-CSF cultures had low levels of MHC class II costimulation/activation molecules, were able to take up mannosylated bovine serum albumin more efficiently than GM + IL-4 DCs, and were poor T-cell stimulators. The two DC populations migrated to the spleen and pancreas after intravenous injection. To determine the ability of the two DC populations to modulate diabetes development, DCs were pulsed with a mixture of three islet antigen-derived peptides or with medium before injection into prediabetic NOD mice. Despite phenotypic and functional differences in vitro, both populations prevented in vivo diabetes development. Pulsing of the DCs with peptide in vitro did not significantly improve the ability of DCs to prevent disease, which suggests that DCs may process and present antigen to T-cells in vivo. In addition, we detected GAD65 peptide-specific IgG1 antibody responses in DC-treated mice. Overall, these results suggest that a Th2 response was generated in DC-treated mice. This response was optimal when using GM + IL-4 DCs, which suggests that the balance between regulatory Th2 and effector Th1 cells may have been altered in these mice.

Animals↗
PubMed1996

Functional consequences of the binding of MHC class II-derived peptides to MHC class II.

Three MHC class II-derived synthetic peptides (I-A beta (g7)1-16, I-A beta (g7)52-77 and I-A alpha (g7)63-82YC) were analyzed for their ability to bind to syngeneic and allogeneic MHC class II molecules using a whole cell, competitive peptide binding assay. These studies demonstrated that the A beta (g7)1-16 peptide was able to specifically bind to syngeneic as well as to four allogeneic MHC class II molecules. The A alpha (g7)63-82YC peptide bound to self MHC class II molecules with a lower relative affinity and was able to bind to three out of the four allogeneic cells tested. The binding of the three I-A(g7)-derived peptides to the self MHC class II was functionally significant. The A beta (g7)1-16 and A beta (g7)52-77 peptides inhibited the proliferation of a heat shock protein 60 peptide-specific Th1 clone by MHC blockade. Interestingly, the A alpha (g7)63-82YC peptide appeared to interact directly with T cells as pretreatment of the Th1 clone with this peptide resulted in inhibition of antigen-induced proliferation. This phenomenon was analyzed in more detail and it was found that this peptide could behave as a partial agonist. Incubation of T cells with the A alpha (g7)63-82YC peptide resulted in up-regulation of IL-2R alpha chain expression and induction of IFN-gamma secretion. In addition T cells pretreated with this peptide were rendered hyporesponsive to further antigenic stimulation. Thus, a peptide derived from MHC class II may be used in an immunoregulatory capacity.

ATP-Binding Cassette Transporters↗