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See detailEuro-Thymaide - Final publishable report
Geenen, Vincent ULg

Report (2010)

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See detailReconstitution du système immunitaire après allogreffe de cellules souches hématopoïétiques
Castermans, Emilie ULg; Hannon, Muriel ULg; Drion, Pierre ULg et al

in Revue Médicale de Liège (2009), 64(S1), 2-8

Allogeneic hematopoietic stem cell transplantation (alloHCT) is frequently used as treatment for patients with hematological malignancies. Its efficacy depends in part on the destruction of recipient ... [more ▼]

Allogeneic hematopoietic stem cell transplantation (alloHCT) is frequently used as treatment for patients with hematological malignancies. Its efficacy depends in part on the destruction of recipient tumors cells by donor immune cells contained in the graft (graft-versus-tumor effects), underlying the interest of stydying donor immune recovery after alloHCT. Further, donor immune cells play an important role in the prevention and treatment of infections after allHCT, and are the cause of graft-versus-host disease (GVHD). This article reviews the mechanisms of immune recovery after allogeneic hematopoietic cell transplantation (alloHCT), as well as techniques currently used to monitor immune function following allHCT. [less ▲]

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See detailOxytocin: From milk ejection to maladaptation in stress response and psychiatric disorders. A psychoneuroendocrine perspective.
Scantamburlo, Gabrielle ULg; Ansseau, Marc ULg; Geenen, Vincent ULg et al

in Annales d'Endocrinologie (2009), 70(6), 449-54

Oxytocin (OT) is implicated in stress reduction as well as in social behavior. It inhibits the stress-induced activity of the hypothalamic-pituitary adrenal axis responsiveness. OT is involved in social ... [more ▼]

Oxytocin (OT) is implicated in stress reduction as well as in social behavior. It inhibits the stress-induced activity of the hypothalamic-pituitary adrenal axis responsiveness. OT is involved in social affiliation, sexual and maternal-infant binding, anxiety, mood, feeding control and memory. Several lines of evidence suggest a role of OT in psychiatric disorders. Various psychiatric disorders are strongly influenced by social variables, such as panic attacks, depression and early childhood autism, and seem to exhibit a particularly close connection with the brain dynamics that underlie social emotions. This paper proposes an overview of OT in psychiatric disorders through the links with the stress response and prosocial behavior. [less ▲]

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See detailImpact of growth hormone (GH) deficiency and GH replacement upon thymus function in adult patients.
Morrhaye, Gabriel ULg; Kermani, Hamid; Legros, Jean-Jacques ULg et al

in PLoS ONE (2009), 4(5), 5668

BACKGROUND: Despite age-related adipose involution, T cell generation in the thymus (thymopoiesis) is maintained beyond puberty in adults. In rodents, growth hormone (GH), insulin-like growth factor-1 ... [more ▼]

BACKGROUND: Despite age-related adipose involution, T cell generation in the thymus (thymopoiesis) is maintained beyond puberty in adults. In rodents, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and GH secretagogues reverse age-related changes in thymus cytoarchitecture and increase thymopoiesis. GH administration also enhances thymic mass and function in HIV-infected patients. Until now, thymic function has not been investigated in adult GH deficiency (AGHD). The objective of this clinical study was to evaluate thymic function in AGHD, as well as the repercussion upon thymopoiesis of GH treatment for restoration of GH/IGF-1 physiological levels. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-two patients with documented AGHD were enrolled in this study. The following parameters were measured: plasma IGF-1 concentrations, signal-joint T-cell receptor excision circle (sjTREC) frequency, and sj/beta TREC ratio. Analyses were performed at three time points: firstly on GH treatment at maintenance dose, secondly one month after GH withdrawal, and thirdly one month after GH resumption. After 1-month interruption of GH treatment, both plasma IGF-1 concentrations and sjTREC frequency were decreased (p<0.001). Decreases in IGF-1 and sjTREC levels were correlated (r = 0.61, p<0.01). There was also a decrease in intrathymic T cell proliferation as indicated by the reduced sj/beta TREC ratio (p<0.01). One month after reintroduction of GH treatment, IGF-1 concentration and sjTREC frequency regained a level equivalent to the one before GH withdrawal. The sj/beta TREC ratio also increased with GH resumption, but did not return to the level measured before GH withdrawal. CONCLUSIONS: In patients with AGHD under GH treatment, GH withdrawal decreases thymic T cell output, as well as intrathymic T cell proliferation. These parameters of thymus function are completely or partially restored one month after GH resumption. These data indicate that the functional integrity of the somatotrope GH/IGF-1 axis is important for the maintenance of a normal thymus function in human adults. TRIAL REGISTRATION: ClinicalTrials.gov NTC00601419. [less ▲]

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See detailAire and Foxp3 expression in a particular microenvironment for T-cell differentiation
Hansenne, Isabelle; Louis, Céline; Martens, Henri ULg et al

in Neuroimmunomodulation (2009), 16

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See detailThymus dysfunction in the development of type 1 diabetes and endocrine autoimmune diseases
Geenen, Vincent ULg; Dardenne Olivier

in European Endocrinology (2009), 5

The discovery that thymic epithelium from many species expresses a large repertoire of genes encoding neuroendocrine and other tissue-restricted antigens has radically changed our knowledge of the ... [more ▼]

The discovery that thymic epithelium from many species expresses a large repertoire of genes encoding neuroendocrine and other tissue-restricted antigens has radically changed our knowledge of the pathogenic mechanisms underlying the development of organ-specific autoimmune diseases such as type 1 diabetes and autoimmune endocrine diseases. Rather than a breakdown of immunological selftolerance in periphery, there is mounting evidence that the diabetogenic autoimmune response may first arise from a thymus dysfunction in the central programming of β-cell self-tolerance. Insulin-like growth factor 2 (IGF-2) is the dominant member of the insulin gene/protein family expressed in thymic epithelial cells (TECs) from different species, and Igf2-/- mice fail to programme complete tolerance to insulin. Based on the homology between insulin, the primary and immunogenic auto-antigen of type 1 diabetes, and IGF-2, the tolerogenic self-antigen of the insulin family, the design of a regulatory/negative self-vaccination for prevention against type 1 diabetes has been proposed and is under development. [less ▲]

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See detailIntegrity of the somatotrope GH/IGF-1 axis is required for normal thymus function: a clinical study in patients with adult GH deficiency
Morrhaye, Gabriel ULg; Kermani, Hamid; Cheynier, Rémi et al

in The Endocrine Society (Ed.) Proceedings of the 2009 Annual Meeting of the Endocrine Society (2009)

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See detailLes glucocorticoïdes, de puissants immunomodulateurs naturels
Geenen, Vincent ULg

Conference given outside the academic context (2008)

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See detailCoxsackievirus B4 Infection of Murine Foetal Thymus Organ Cultures
Brilot, F.; Jaidane, H.; Geenen, Vincent ULg et al

in Journal of Medical Virology (2008), 80(4), 659-66

The infection of foetal thymus with coxsackievirus B4 (CV-B4) E2 has been studied ex vivo by using CD-1 mice on foetal day 14, as a ready source of organs for experimentation to investigate the hypothesis ... [more ▼]

The infection of foetal thymus with coxsackievirus B4 (CV-B4) E2 has been studied ex vivo by using CD-1 mice on foetal day 14, as a ready source of organs for experimentation to investigate the hypothesis of the role of thymic viral infections in the pathogenesis of type 1 diabetes. The replication of CV-B4 E2 in murine foetal thymus organ cultures has been demonstrated by evaluating the levels of positive- and negative-stranded viral RNA in cells by using a real-time quantitative RT-PCR method and by determining titres of infectious viral particles in culture supernatants for 7 days post-infection (p.i.). Staining of tissue sections with an anti-cytokeratin antibody and haematoxylin-eosin showed that CV-B4 infection had no visible effect on cell survival and organ integrity. Cell counts in mock- and virus-infected foetal thymus organ cultures increased from day 1 through day 7, and live cell numbers were comparable in both conditions as shown by Trypan blue exclusion test and 7-amino-actinomycin D staining of thymocytes. Compared with controls on day 7 p.i., cytofluorometric analyses on cells from CV-B4 E2-infected foetal thymus organ cultures displayed a marked increase in the percentage of the most immature CD3(-)CD4(-)CD8(-) thymocytes, and a decrease in the percentage of immature CD3(-)CD4(+)CD8(+) cells, together with an increase in the percentage of mature CD3(+)CD4(+) and CD3(+)CD8(+) cells. These data show that CV-B4 E2 disturbs T-cell maturation and differentiation processes in infected murine foetal thymus organ cultures and provide evidence of a suitable system to investigate the effect of viruses in T-cell differentiation. J. Med. Virol. 80:659-666, 2008. (c) 2008 Wiley-Liss, Inc. [less ▲]

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See detailEvidence for neo-generation of T cells by the thymus after non-myeloablative conditioning.
Castermans, Emilie ULg; Baron, Frédéric ULg; Willems, Evelyne ULg et al

in Haematologica (2008), 93(2), 240-7

BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning ... [more ▼]

BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning. DESIGN AND METHODS: Fifty patients were randomized to receive either CD8-depleted (n=22) or non-manipulated (n=28) peripheral blood stem cells. The median patients age was 57 (range 36-69) years. The conditioning regimen consisted of 2 Gy total body irradiation with or without added fludarabine. Twenty patients received grafts from related donors, 14 from 10/10 HLA-allele matched unrelated donors, and 16 from HLA-mismatched unrelated donors. Graft-versus-host disease pro-phylaxis consisted of mycophenolate mofetil and cyclosporine. Immune recovery during the first year after hematopoietic cell transplantation was assessed by flow cytometry phenotyping, analyses of the diversity of the TCRBV repertoire, and quantification of signal-joint T-cell receptor excision circles (sjTREC). RESULTS: CD8-depletion of the graft reduced the recovery of CD8(+) T-cell counts in the first 6 months following transplantation (p<0.0001) but had no significant impact on the restoration of other T-cell subsets. Both sjTREC concentration and CD3(+) T-cell counts increased significantly between day 100 and 365 (p=0.010 and p=0.0488, respectively) demonstrating neo-production of T cells by the thymus. Factors associated with high sjTREC concentration 1 year after transplantation included an HLA-matched unrelated donor (p=0.029), a high content of T cells in the graft (p=0.002), and the absence of chronic graft-versus-host disease (p<0.0001). CONCLUSIONS: Our data suggest that while immune recovery is mainly driven by peripheral expansion of the graft-contained mature T cells during the first months after non-myeloablative transplantation, T-cell neo-generation by the thymus plays an important role in long term immune reconstitution in transplanted patients. [less ▲]

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See detailHLA genetics in 'latent' autoimmune diabetes of adults (LADA)
Geenen, Vincent ULg

in International Diabetes Monitor (2008), 20

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See detailLes cibles hormonales de la réponse auto-immune
Geenen, Vincent ULg

in Annales d'Endocrinologie (2008), 69

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See detailA defect of thymus-dependent self-tolerance to insulin-secreting ß cells in the pathogenesis of type 1 diabetes
Hansenne, Isabelle; Louis, Céline; Geenen, Vincent ULg

in Pontell, E. B. (Ed.) Immune Tolerance Research Developments (2008)

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See detailHistoire de la recherche biomédicale
Geenen, Vincent ULg

Learning material (2007)

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See detailIgf2 expression is required for complete immunological tolerance to insulin
Hansenne, Isabelle; Renard, Chantal; Geenen, Vincent ULg

Poster (2007, July)

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See detailEvaluation clinique de la fonction du thymus.
Castermans, Emilie ULg; Morrhaye, Gabriel ULg; Marchand, S. et al

in Revue Médicale de Liège (2007), 62(11), 675-8

The essential role of the thymus is to install an extremely diverse repertoire of T lymphocytes that are self-tolerant and competent against non-self, as well as to generate self-antigen specific ... [more ▼]

The essential role of the thymus is to install an extremely diverse repertoire of T lymphocytes that are self-tolerant and competent against non-self, as well as to generate self-antigen specific regulatory T cells (Treg) able to inactivate in periphery self-reactive T cells having escaped the thymic censorship. Although indirect, techniques of medical imaging and phenotyping of peripheral T cells may help in the investigation of thymic function. Nowadays however, thymopoiesis is better evaluated through quantification by PCR of T-cell receptor excision circles (TREC) generated by intrathymic random recombination of the gene segments coding for the variable parts of the T-cell receptor for antigen (TCR). The TREC methodology is very valuable in the circumstances not associated with intense proliferation or apoptosis of peripheral T lymphocytes. [less ▲]

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