The effect of environmental factors on development of high affinity CTL was investigated using a system whereby OT-1 cells were primed in vitro by engineered APC. After a 20 h priming phase, CTL were transferred to recipient mice that were either naïve, or had been injected with activated dendritic cells one day earlier, thus creating a reactive lymph node.

In order to identify the APCs that were responsible for the development of this state of immune tolerance, we aimed to generate a transgenic mouse that express a recombinant fluorescent protein in the mammary glands, an approach that should result in high levels of expression of the fluorescent protein in the milk. We thus should be able to detect the cells that capture, degrade and present this antigen to T cells. Since we had previously generated a monoclonal antibody, 2C44, that reacts to a peptide derived from the Leishmania LACK protein bound to I-Ad MHC ...

We found that CCR6–deficient (CCR6-KO) mice were resistant to induction of EAE but became susceptible when transferred with small number of CCR6-sufficient T cells. CCR6 was found to be required on a first wave of TH-17 cells that entered the CNS through the choroid plexus epithelial cells, which constitutively expressed CCL20 in both mice and humans.

Subcutaneous injection of hypoxic DCs into the footpads of mice results in defective DC homing to draining lymph nodes, but enhanced leukocyte recruitment at the site of injection.

Tumor growth is supported by tumor stroma, such as tumor associated macrophages (TAM) and tumor associated dendritic cells (TADC). We have recently reported that TAM display massive nuclear localization of the p50 NF-kB inhibitory homodimer, which correlates with impaired inflammatory functions.The functional significance of this observation was demonstrated in p50 NF-kB deficient mice, which displayed tumor growth inhibition.

We infected mice with CD8+ T-cells primed with or without the influence of a reactive lymph node with a flu-virus encoding the specific antigen. After several days we determined the viral load in the lungs with RT-PCR. The results show that in mice with CD8+ T-cells primed with a reactive lymph node the viral load in the lungs was significantly smaller then in a control mice.

These K/O mice were studied with regard to responses to viral infections. We used the mouse pox virus Ectromelia and MVA-BN. Coinfection with MVA-BN and Ectromilia protected the IFNalpha receptor -/- mice. The data show that MVA-BN can induce potent innate immune responses able to control viral replication to allow the specific immune response to eliminate Ectromelia in immune deficient mice.

Hu-SCID mice were used to study responses to EBV and HIV.

IDO appears critical for the regulation of TNBS colitis upon CTLA-4 engagement, as the beneficial effect of anti-CTLA-4 treatment was lost in IDO-deficient mice. By contrast, the absence of IDO did not alter the course of inflammation in mice injected with TNBS only, an unexpected finding which suggests that IDO-dependent counter-regulation requires other factors/cells in addition to IDO production and T cell activation by TNBS.

We showed that, in the absence of adjuvants, DEX mediate potent antigen dependent-antitumor effects against preestablished tumors in mice pretreated with immunopotentiating dosing of cyclophosphamide (CTX).

We found that the cooperation between IFNalpha,beta and Flt3L (FL) plays an important role in the defense against Herpes simplex virus type 1 (HSV-1) in neonates. Treatment of neonatal mice with recombinant IFNalpha has a short-term, FL-independent and a long-term, FL-dependent protective effect against HSV-1. In mice lacking FL, neonatal resistance against HSV-1 is very low and DC numbers in the spleen are reduced. In C57BL/6 mice, treatment with rIFNalpha at birth induced both FL and plasmacytoid DC (pDC) that resulted in enhanced resistance against HSV-...

We found that the cooperation between IFNalpha,beta and Flt3L (FL) plays an important role in the defense against Herpes simplex virus type 1 (HSV-1) in neonates. Treatment of neonatal mice with recombinant IFNalpha has a short-term, FL-independent and a long-term, FL-dependent protective effect against HSV-1. In mice lacking FL, neonatal resistance against HSV-1 is very low and DC numbers in the spleen are reduced. The treatment of these mice with rIFNalpha at day 6 resulted in an increased resistance against infection with HSV-1 at day 7. In C57BL/6 mice, tr...

The immunotherapy potential of DC, pulsed with tumor antigens, was evaluated in EG7-OVA and P815 tumor models. Depletion of natural regulatory T cells in these tumor bearing mice resulted in rejection of P815 cells, but not EG7-OVA, suggesting that regulatory T cells have a stronger impact on immune responses against weakly immunogenic or auto-antigen (P1A).

We have immunized mice with human DC derived-exosomes and generated hybridomas that produce antibodies recognizing at least the human exosomes.

These mice were used in a DC staining experiment. We have started to visualize and characterize the DC which carry I-Ad/LACK complexes at the cell surface in BALB/c mice infected by leishmania major.

These not immunized mice were used in a DC staining experiment. To investigate whether several mAb could be used to detect APC presenting LACK in vivo, BALB/c mice were immunized or not with either LACK or OVA. LN cells were purified 2 days later, and stained with either 2C44, 2F74, 2E60 or 2X8 mAb. None of these mAb stained DC purified from non immunized mice. However, among the 4 mAb, only 2C44 could stain DC in LACK-immunized mice, but not in OVA-immunized mice. Furthermore, 2C44 stained DC from LACK-immunized mice expressing the H2-d haplotype but did no...

The effect of environmental factors on development of high affinity CTL was investigated using a system whereby OT-1 cells were primed in vitro by engineered APC. After a 20 h priming phase, CTL were transferred to recipient mice that were either naïve, or had been injected with activated dendritic cells one day earlier, thus creating a reactive lymph node.

These mice were generated with the intention to elucidate in vivo DC developmental regions in steady state and inflammation in situ.

The animal(s) were immunized in vivo with in vitro matured DC and / or treated using a maturation signal.

By immunizing mice with ovalbumin-conjugated anti-Siglec-H Ab in the presence of CpG, we demonstrated generation of antigen-specific CD8 T cells in vivo.