Aire and Foxp3 expression in a particular microenvironment for T-cell differentiation

in Neuroimmunomodulation (2009), 16

Integrity of the somatotrope GH/IGF-1 axis is required for normal thymus function: a clinical study in patients with adult GH deficiency

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

Coxsackievirus B4 Infection of Murine Foetal Thymus Organ Cultures

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 ▲]

Evidence for neo-generation of T cells by the thymus after non-myeloablative conditioning.

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 ▲]

Les cibles hormonales de la réponse auto-immune

in Annales d'Endocrinologie (2008), 69

Histoire de la recherche biomédicale

Learning material (2007)

The central role of thymus-dependent tolerance to islet ß cells: a way for the development of a negative self-vaccine against type 1 diabetes

Conference (2007, February)

Evaluation clinique de la fonction du thymus.

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 ▲]

Dialogue between Blastocyst hCG and Endometrial LH/hCG Receptor: Which Role in Implantation?

in Gynecologic & Obstetric Investigation (2007), 64(3), 156-60

The specific interaction of blastocyst-derived human chorionic gonadotropin (hCG) and endometrial LH/hCG-R constitutes a fundamental component of the molecular dialogue at the materno-fetal interface ... [more ▼]

The specific interaction of blastocyst-derived human chorionic gonadotropin (hCG) and endometrial LH/hCG-R constitutes a fundamental component of the molecular dialogue at the materno-fetal interface. From our observations and studies from other groups, hCG was indeed shown to play a significant role in implantation and tolerance of the embryo, decidual differentiation and remodeling, as well as in placentation. The profile pattern of LH/hCG-R expression by endometrial epithelium correlates with the theoretical timing of the implantation window. Studies are currently being conducted in assisted medical procreation and in an animal model of implantation to establish the index of LH/hCG-R expression as a new biomarker of uterine receptivity for embryo implantation. [less ▲]

La voie du thymus et de la tolérance centrale au soi dans le développement d'une self-vaccination négative contre le diabète de type 1

Conference (2006, December)