Identification of the peripheral niche controlling CD4 homeostatic proliferation

La greffe de cellules souches hématopoïétiques représente la meilleure option thérapeutique pour plusieurs patients atteints de leucémie agressive. Malheureusement, la reconstitution immunitaire des lymphocytes T, particulièrement celle des lymphocytes T CD4+, peut prendre plusieurs mois ou plusieurs années à survenir. Pendant cette période de lymphopénie profonde, les patients sont susceptibles de développer des complications infectieuses ou rechuter de leur leucémie. La régénération des lymphocytes peut s’effectuer par thymopoïèse via la prolifération homéostatique (PH) des lymphocytes T matures du greffon. Cependant, dans la majorité des contextes cliniques de lymphopénie humaine, la thymopoïèse est dysfonctionnelle et la régénération des lymphocytes T doit s’effectuer par la PH. Alors que la PH est normalement suffisante pour régénérer les lymphocytes T CD8+, elle est insuffisante pour restaurer le nombre de lymphocytes T CD4+ en périphérie. L’interleukine-7 (IL-7) et le complexe majeur d'histocompatibilité de classe II (CMH II) exprimé par les cellules présentatrices d’antigènes (CPA) sont essentiels pour la PH des lymphocytes T CD4+.Le but de mon projet de maîtrise était d'identifier le(s) type(s) de CPA qui régule(nt) la PH des lymphocytes T CD4+ naïfs. À l’aide de transferts adoptifs de lymphocytes T dans des souris lymphopéniques qui présentaient des déficiences pour certains types de CPA, nous avons montré que les cellules dendritiques (DC) CD11c+ étaient essentielles pour la PH de cellules T CD4+. Étonnamment, la déplétion sélective des DC CD8a+, ou DC plasmacytoïdes (pDC) ou des deux types de DC en même temps n’était pas suffisante pour diminuer la PH des lymphocytes T CD4+. Jusqu'à présent, nos données supportent un modèle où les DC CD8a+ et les pDC ne seraient pas essentielles à la PH des lymphocytes T CD4+ chez une souris lymphopénique. Par contre, la déplétion sélective de ces 2 types de DC se traduit par une diminution significative du nombre de cellules T CD4+. Des études supplémentaires sont nécessaires pour déterminer le rôle potentiel des DC conventionnelles CD11b+CD11c+ dans l'homéostasie des lymphocytes T CD4+.Hematopoietic stem cell transplantation represents the best therapeutic option for patients with aggressive leukemia. Unfortunately, side effects are numerous and lymphocytes regeneration can take several months or years to occur. During this period of profound lymphopenia, patients are at higher risk of developing infectious complications or relapse from their disease. Lymphocyte regeneration can occur via thymopoiesis which recapitulates T cell production as it occurs early in life or via homeostatic proliferation (HP) of mature T cells in the graft. However, in most clinical settings of human lymphopenia, thymopoiesis is dysfunctional and T cell regeneration largely depends on HP. While HP is typically sufficient for CD8 regeneration, it is insufficient for restoring naïve CD4 counts. Access to IL-7 and major histocompatibility complex class II (MHCII) expressed by antigen presentation cells (APCs) are critical for HP of CD4+ T cells. This project aims to identify the APC subset(s) that control CD4 HP during lymphopenia. Adoptive transfer of T lymphocytes into lymphopenic mice with target APC subsets were utilized in this study. We were able to observe how CD11c+ dendritic cells (DCs) are critical components for HP of CD4+ T cells. Interestingly, the depletion of CD8a+DCs or plasmacytoid DCs (pDCs), or both subsets did not have a significant impact on CD4 proliferation. However, the depletion of CD8a+ DCs or pDCs influenced the CD4 numbers. The findings ultimately support a model where CD8a+ DCs and pDCs are not needed for HP but may affect CD4+ T cells survival during lymphopenia. Further research is needed in order to verify the potential role of CD11b+CD11c+ DCs in CD4 HP

Restoring T cell homeostasis after allogeneic stem cell transplantation; principal limitations and future challenges

For several leukemia patients, allogeneic stem cell transplantation (allogeneic-SCT) is the unique therapeutic modality that could potentially cure their disease. Despite significant progress made in clinical management of allogeneic-SCT, acute graft-versushost disease (aGVHD) and infectious complications remain the second and third cause of death after disease recurrence. Clinical options to restore immunocompetence after allogeneic-SCT are very limited as studies have raised awareness about the safety with regards to graft-versus-host disease (GVHD). Preclinical works are now focusing on strategies to improve thymic functions and to restore the peripheral niche that have been damaged by alloreactive T cells. In this mini review, we will provide a brief overview about the adverse effects of GVHD on the thymus and the peripheral niche and the resulting negative outcome on peripheral T cell homeostasis. Finally, we will discuss the potential relevance of coordinating our studies on thymic rejuvenation and improvement of the peripheral lymphoid niche to achieve optimal T cell regeneration in GVHD patients

Preparation of chemically reduced graphene oxide reinforced Epoxy Resins polymer as a composite for electromagnetic interference shielding and microwave absorbing applicationns

The preparation of chemically reduced graphene oxide (rGO) and the optimization of epoxy resins’ properties using micro or nanofillers are now common practices. rGO nanoparticles (60 nm) based on an epoxy resin polymer were prepared at the concentrations of 0, 1, 2, 3, 4, and 5% weight percentage with fixed 6-mm thicknesses. The dielectric properties of the composites were measured by the reflection/transmission technique in connection with a vector network analyser (VNA) at a frequency range of 8–12 GHz. The microwave absorption and shielding effectiveness properties were calculated by using the reflection S₁₁ and transmission S21 results. The microstructure and morphology of the polymer and the rGO/cured epoxy composites were studied by field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared (FT-IR) spectroscopy, and the X-ray Diffraction (X-RD) technique for characterizing crystalline materials. The dielectric and other properties of the rGO/cured epoxy composites were investigated based on the filler load and frequency. It was found that the applied frequency and the filler concentrations affected the dielectric properties of the rGO/cured epoxy composites. The results showed that the introduction of rGO particles to the composites increased their dielectric properties smoothly. The study of the dependence on frequency of both the dielectric constant ε′ and the dielectric loss ε″ showed a decrease in both quantities with increasing frequency, indicating a normal behaviour of the dielectrics. Cole–Cole plots were drawn with ε′ and ε″. A theoretical simulation in terms of the Cole–Cole dispersion law indicates that the Debye relaxation processes in the rGO/cured epoxy composites are improved due to the presence of the rGO filler. Moreover, with the addition of rGO as a filler into the Epoxy matrix, it now exhibits promise as a lightweight material for microwave absorption as well as an effective electromagnetic interference (EMI) shielding material