Chantal Denys
Université libre de Bruxelles
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Featured researches published by Chantal Denys.
Transplantation | 1996
Michel Toungouz; Chantal Denys; Etienne Dupont
The mechanism of action of intravenous immunoglobulins (IVIg) for prevention of graft rejection and graft-versus-host disease (GVHD) is poorly understood. Recently, it has been shown that these preparations contain natural antibodies directed toward interferon (IFN)-gamma. During mixed lymphocyte reaction (MLR), which constitutes an in vitro model of allograft rejection and GVHD, T cell recognition of HLA differences induces IFN-gamma release. This cytokine promotes T cell proliferation and acts as a macrophage-activating factor to provoke tumor necrosis factor-alpha secretion. The aim of the present work is to investigate the influence of IVIg on IFN-gamma production occurring during MLR and its subsequent impact on T cell proliferation and tumor necrosis factor (TNF)-alpha secretion. We tested IVIg preparations for the presence of anti-IFN-gamma and anti-TNF-alpha antibodies. High amounts of anti-IFN-gamma, but not anti-TNF-alpha antibodies, were found. IVIg addition at the initiation of culture resulted in IFN-gamma secretion blockade. Likewise, lymphocyte proliferation and TNF-alpha secretion were inhibited. This inhibition was reversed by the addition of recombinant human IFN-gamma. Furthermore, the inhibitory properties of IVIg were mimicked by an IFN-gamma-specific neutralizing monoclonal antibody. We conclude that the capacity of IVIg to inhibit proliferation and TNF-alpha release during MLR is due to IFN-gamma blockade by natural antibodies. This immunosuppressive mechanism could contribute to the effect of IVIg on prophylaxis of organ graft rejection and GVHD after allogeneic bone marrow transplantation.
Transplantation | 1996
Michel Toungouz; Chantal Denys; Donat De Groote; Marc Andrien; Etienne Dupont
Interleukin (IL)-10 is an immunosuppressive cytokine potentially involved in the control of the allogeneic response. Several studies failed to detect it in mixed lymphocyte reaction supernatants. However, experiments using IL-10-specific antibodies, revealing its inhibitory action on interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, provided indirect evidence that endogenous IL-10 was produced. The aim of the present work is to elucidate the role of IL-10 during mixed lymphocyte reaction and to investigate the influence of HLA-DR antigens on its production and on the regulatory loop involving TNF-alpha and IFN-gamma. Using a highly sensitive ELISA, a significant (P < 0.0001) but low IL-10 release could be detected (33.7 +/- 3.6 pg/ml) in response to HLA-DR disparities. However, IL-10 release was not graded as 1 DR mismatch (MM)-induced maximal secretion (32.3 +/- 5.1 pg/ml). This contrasted with TNF-alpha and IFN-gamma productions, which significantly increased in 2 DR MM pairs. Addition to IL-10-specific antibodies resulted in higher enhancement of INF-gamma (235 +/- 38% vs. 122 +/- 39%, P = 0.02) and, to a lesser extent, TNF-alpha (147 +/- 56% vs. 112 +/- 20%, NS) in 1 compared with 2 DR MM pairs. We conclude that the 1 DR MM setting is associated with optimal IL-10 secretion and more efficient inhibition of IFN-gamma and TNF-alpha compared with the 2 DR MM configuration. Although promoting enhanced IFN-gamma and TNF-alpha release, introduction of an additional DR MM does not result in increased IL-10 production. These data indicating that the IL-10 regulatory feedback loop is more effective in 1 DR rather than complete DR incompatibility could have an impact on matching policies for planned transfusion.
Vox Sanguinis | 1997
Chantal Denys; Michel Toungouz; Etienne Dupont
Background and objectives: We previously found that interferon‐γ (IFN‐γ) antibodies in intravenous immunoglobulins (IVIG) can block not only IFN‐γ production and tumor necrosis factor‐α secretion, but also T‐cell proliferation. Since the presence of IFN‐γ antibodies has been attributed to previous viral infection, we hypothesized that the viral status of the plasma donors used for IVIG pools might be a decisive factor in controlling the immunosuppressive capacity of IVIG. Materials and methods: We tested three different pooled, human IVIG preparations for the presence of IFN‐γ antibodies by ELISA. Results: Comparison of the immunomodulatory activity of polyvalent IVIG with that of specific CMV and HBs IVIG showed that the latter had higher levels of IFN‐γ antibodies and an increased capacity to block mixed lymphocyte reaction and cytokine production. Conclusion: We propose that these in vitro assays constitute a basis for the selection of plasma intended for manufacturing IVIG aimed at immunosuppression in the transplant setting.
Human Immunology | 1995
Michel Toungouz; Chantal Denys; Marc Andrien; Donat De Groote; Etienne Dupont
We investigated the genetic control of IFN-gamma release during MLR and its relationship with TNF-alpha and IL-12. Blocking experiments demonstrated the IFN-gamma dependence of TNF-alpha production and the significant contribution of IL-12 to IFN-gamma secretion. We studied informative pairs allowing the evaluation of the relative importance of HLA class I and class II antigens. Maximal IFN-gamma secretion allowing discrimination between fully HLA different and identical subjects required 5 days. In class I different but DRB1 identical pairs, a moderate but discriminant IFN-gamma release was found. Exogenous IL-12 addition after 24 hours of preactivation by MLR resulted in a marked enhancement of IFN-gamma production at day 2. In pairs differing only by class I antigens, the discriminating capacity was significantly increased as compared to values obtained in absence of IL-12 at day 2 (p < 0.004) and at day 5 (p < 0.004). The crucial role of class I antigens on IFN-gamma release was further substantiated by the blocking action of the W6/32 mAb directed against a monomorphic epitope common to all HLA-A, -B, and -C antigens. We conclude that IFN-gamma production during MLR is under the control of class I antigens. Furthermore, exogenous IL-12 strongly amplifies their influence.
Human Immunology | 1993
Michel Toungouz; Chantal Denys; Donat De Groote; Marc Andrien
We tested various factors affecting the production of the CKs IL-6 and TNF-alpha during in vitro alloactivation induced by MLR. Different MLR combinations involving familial and unrelated pairs were evaluated. In family studies, MLRs involving pairs of HLA-identical siblings (n = 6) were characterized by IL-6 and TNF-alpha secretion comparable to the one of autologous controls, in marked contrast with HLA-different combinations (n = 6). These displayed a strong and early (day 3) release of both CKs. In combinations of unrelated individuals involving HLA-A, -B, -C-different but -DR, -DQ-identical pairs (n = 3), low CK release was observed. Addition of LPS (1 micrograms/ml) considerably increased production of IL-6 and TNF-alpha. Clear discrimination of MHC class II differences required a 24-hour preculture followed by addition of LPS for 4 hours, a time relationship compatible with a priming phenomenon due to alloactivation. We conclude that MHC class II alloactivation not only provokes IL-6 and TNF-alpha secretion, but also primes macrophages to LPS so that the production of these CKs is markedly increased and occurs much earlier after LPS addition.
Hepatology | 1991
Jacques Devière; Jean-Pierre Vaerman; Chantal Denys; Liliane Schandené; Paul Vandenbussche; Yves Sibille; Etienne Dupont
British Journal of Haematology | 2008
Michel Toungouz; Chantal Denys; Donat De Groote; Etienne Dupont
Transplantation | 1994
Michel Toungouz Nevessignsky; Chantal Denys; Marc Andrien; Donat De Groote; Etienne Dupont
Transplantation proceedings | 1995
Michel Toungouz; Chantal Denys; Marc Andrien; Etienne Dupont
Transplantation Proceedings | 1997
Michel Toungouz; Chantal Denys; Etienne Dupont