The cross-talk between dendritic and regulatory T cells: good or evil?

in Journal of Leukocyte Biology (2007), 82(4), 781-94

Immune responses against pathogens require fine regulation in order to avoid excessive inflammation, which could be harmful to the host. Moreover, the immune system must be tolerant to non-pathogenic ... [more ▼]

Immune responses against pathogens require fine regulation in order to avoid excessive inflammation, which could be harmful to the host. Moreover, the immune system must be tolerant to non-pathogenic antigens in order to prevent allergy, autoimmunity and transplant rejection. There is accumulating evidence that interactions between dendritic cells (DC) and regulatory T (Treg) cells play a crucial role in the balance between immune response and tolerance. Communications between these cells are complex, bi-directional and mediated by soluble or cell surface molecules. The maturation status of DC, which may be influenced by different microenvironmental factors, is considered as an important checkpoint for the induction of peripheral tolerance through modifications of the activation status of T cells. Moreover, several lines of experimental evidence suggest that different subsets or the functional status of DC are also involved in the promotion of Treg cell differentiation. A better knowledge of the regulatory mechanisms of the immune response induced or inhibited by DC via their interactions with Treg cells could be relevant for the development of new immunotherapeutic approaches. [less ▲]

NK Cells Interact With virus–like particles (VLP) of human papillomavirus (HPV)

Conference (2007, June 01)

NK CELLS and virus–like particle (VLP) of human papillomavirus (HPV)

Conference (2007, April 25)

Association between Epstein-Barr virus and Hodgkin's lymphoma in Belgium: A pathological and virological study

in Leukemia & Lymphoma (2007), 48(7), 1323-1331

The association between Epstein-Barr virus (EBV) and classical Hodgkin's lymphoma (cHL) varies according to the geographic location. In this work we sought to characterize EBV involvement in a series of ... [more ▼]

The association between Epstein-Barr virus (EBV) and classical Hodgkin's lymphoma (cHL) varies according to the geographic location. In this work we sought to characterize EBV involvement in a series of 111 cHL cases diagnosed in Belgium. The overall prevalence of EBV infection detected by in situ hybridization in Reed-Sternberg cells was 33%. EBV positivity correlated with older age at diagnosis (454 years; p = 0.01), mixed cellularity subtype (p = 0.000001), male gender (p = 0.004) and tended to be associated with higher clinical stage (III/IV; p = 0.02). The molecular features of the virus in EBV-positive cHL were studied by comparison with a series of reactive tonsils. A 30-bp deletion within the LMP-1 gene was in 15/28 (53.6%) EBV-positive cHL cases, and in 41.7% of reactive tonsil samples. This variant did not correlate with any clinical or pathological feature. The EBV strain was type A in all cHL and reactive samples. [less ▲]

Le cancer du col de l'utérus: du virus au traitement

in Revue Médicale de Liège (2007), 62(S1)

Squamous cell cancer of the uterine cervix is associated with a high morbidity and mortality worldwide and in Belgium. New therapeutic approaches have been recently proposed. The development of this ... [more ▼]

Squamous cell cancer of the uterine cervix is associated with a high morbidity and mortality worldwide and in Belgium. New therapeutic approaches have been recently proposed. The development of this cancer is related to the infection by oncogenic human papillomavirus (HPV) types. The link between cervical cancer and HPV has, in recent years, generated, a great interest for studies aiming to better understand the role of the immune system in the control of these infections and for the development of prophylactic anti-HPV vaccines. [less ▲]

Defensis induce the recruitment of dendritic cells in cervical human papillomavirus-associated (pre)neoplastic lesions formed in vitro and transplanted in vivo

in FASEB Journal (2007), 21(11), 2765-75

In addition to their direct antimicrobial activity, defensins might also influence adaptive immunity by attracting immature dendritic cells (DC). As these cells have been shown to be deficient in uterine ... [more ▼]

In addition to their direct antimicrobial activity, defensins might also influence adaptive immunity by attracting immature dendritic cells (DC). As these cells have been shown to be deficient in uterine cervix carcinogenesis, we evaluated the ability of -defensin (HNP-2, human neutrophil defensin 2) and ß-defensin (HßD2, human beta defensin 2) to stimulate their migration in human papillomavirus (HPV)-associated (pre)cancers. We first observed, using RT-PCR and immunohistology, that HßD2 is absent in HPV-transformed keratinocytes and that it is weakly expressed in cervical (pre)neoplastic lesions in comparison with normal keratinocytes. We next demonstrated that defensins exert a chemotactic activity for DC in a Boyden Chamber assay and stimulate their infiltration in an in vitro-formed (pre)neoplastic epithelium (organotypic culture of HPV-transformed keratinocytes). To evaluate the ability of defensins also to recruit DC in vivo, we developed a model of immunodeficient mice grafted with organotypic cultures of HPV+ keratinocytes, which form an epithelium similar to a high-grade neoplastic lesion, with tumoral invasion and neovascularization. Intravenously injected human DC were able to infiltrate grafts of HPV+ keratinocytes after administration of HNP-2 in the transplantation chamber. Taken together, these results suggest that defensins could reverse a frequent immune alteration observed in cancer development. [less ▲]

Dendritic Cells: More Than Just Adaptive Immunity Inducers?

in Current Immunology Reviews (2007), 2

Dendritic cells (DC) are well known for their capacity to induce immune responses and there is also accumulating evidence of their ability to interact with various cell types of the innate system, such as ... [more ▼]

Dendritic cells (DC) are well known for their capacity to induce immune responses and there is also accumulating evidence of their ability to interact with various cell types of the innate system, such as NK, NKT or TCR gamma-delta cells. These interactions are bi-directional, mediated by soluble or cell surface molecules and have been mainly described in the context of immune responses to infectious agents and tumors. NK, NKT or TCR gamma-delta cells induce the maturation of DC, as shown by the increased expression of CD86, IL12 production and priming of T cell responses. On the other hand, mature DC have the ability to activate NK, NKT or TCR gamma-delta cells for sustained innate immune responses and activated NK cells may kill immature DC. In addition, DC and NK or TCR gamma-delta cells share similar functions such as cytotoxic and antitumor activity, interferon production and antigen presentation capacity. [less ▲]

Phase I/IIclinical trial of local GM-CSF application in patients with cervical HPV-associated low grade squamous intraepithelial lesions

Conference (2007)

Background: Quantitative and functional alterations of professional antigen-presenting cells (APC) in SIL suggest that these lesions may have a diminished capacity to capture viral antigens. Moreover, GM ... [more ▼]

Background: Quantitative and functional alterations of professional antigen-presenting cells (APC) in SIL suggest that these lesions may have a diminished capacity to capture viral antigens. Moreover, GM-CSF (whose production is decreased in HPV-transformed keratinocytes) is an essential factor for the migration of APC in cervical (pre)neoplastic lesions formed in vitro and transplanted in vivo on mouse. In this study we performed a phase I/II clinical trial in order to determine whether a local application of GM-CSF on cervical low-grade squamous intraepithelial lesions (LSIL) might increase the recruitment of APC into the epithelium and indirectly the viral antigen presentation to the immune system. Methods: Fifteen patients with LSIL (10 GM-CSF and 5 placebo) were enrolled in this study. Patients received 4 GM-CSF applications (or placebo gel) and were followed during 6-7 months. APC infiltration was quantified by immunostaining with anti-CD1a mAb. Cellular immune response was evaluated by using an IFN-gamma intracellular staining on PBMC stimulated in vitro with the E7 HPV16 protein and L1 HPV16 Virus-like particles (VLP). Hybrid capture was performed to semi-quantify the viral DNA in cervical brush specimens. Results: GM-CSF applications were well tolerated in all patients. No difference in the cytological/histological and viral parameters assessed at 2 and 6 months after the last application was observed between the GM-CSF and the placebo group. An increased number of CD1a+ APC was observed in 6/10 patients treated by GM-CSF compared to 1/5 patient in the placebo group. There was an increased immune response against HPV in the GM-CSF group showed by NK and T cells producing IFN-gamma. [less ▲]

Establishment and characterisation of two novel human KSHV- and EBV-negative Burkitt cell lines, GAL-01 and GAL-02, from a primary lymphomatous effusion

in European Journal of Haematology (2006), 77(4), 318-326

Objectives: Burkitt's lymphoma (BL) is a highly aggressive mature B-cell neoplasm comprising endemic, sporadic and immunodeficiency-associated variants. Human cell lines constitute a very useful tool to ... [more ▼]

Objectives: Burkitt's lymphoma (BL) is a highly aggressive mature B-cell neoplasm comprising endemic, sporadic and immunodeficiency-associated variants. Human cell lines constitute a very useful tool to investigate the biology of lymphoid neoplasia. In this study, we succeeded in establishing two human cell lines, GAL-01 and GAL-02, from a HIV-negative patient with Epstein-Barr virus (EBV) -negative sporadic BL presenting as an effusion. GAL-01 and GAL-02 were established at diagnosis and after one course of polychemotherapy, respectively. The in vivo effusion occurred in a very peculiar clinical setting; the patient having a previous history of intestinal diffuse large B-cell lymphoma. Methods: The morphologic, immunophenotypic and molecular genetic features of GAL cell lines are reported and compared with those of the parental tumour. The findings clearly demonstrated that the Burkitt effusion did not represent disease progression of the intestinal tumour, but represented a second primary haematological malignancy. The in vivo tumorigenic properties of the cells were tested by subcutaneous injection to NOD/SCID mice. Results: Both cell lines were composed of medium-sized lymphoid cells with clumped chromatin, multiple medium-sized nucleoli and moderate amounts of vacuolated cytoplasm. GAL cells display the phenotype and genotype of a B-cell lineage (positive for CD20, CD79a and clonal rearrangement of Ig heavy chain), carry the c-MYC rearrangement by t(8;22)(q24;q11) translocation and are characterised by the expression of the germinal centre-associated antigens CD10, BCL6, CD38 and absent to low BCL2 expression. EBV and HHV8 were not identified within parental tumour or in cultured cells. Subcutaneous injection of both cell lines to NOD/SCID mice induced tumour formation. Conclusions: GAL-01 and GAL-02, two novel EBV-negative human BL cell lines represent a potentially useful experimental model to study the biology of BL possibly including the resistance to chemotherapy. [less ▲]

MUCOADHESIVE PHARMACEUTICAL COMPOSITIONS COMPRISING CHEMOATTRACTANTS.

Patent (2006)