Invariant NKT Cells Suppress CD8+ T-Cell–Mediated Allergic Contact Dermatitis Independently of Regulatory CD4+ T Cells

Invariant natural killer T (iNKT) cells expressing a CD1d-restricted invariant αβTCR have key regulatory roles in autoimmunity, pathogen immunity, and tumor surveillance, but their function in the control of allergic skin diseases remains poorly documented. Using a model of contact hypersensitivity (CHS) to the hapten DNFB, we show here that iNKT cell deficiency results in enhanced skin inflammation due to augmented hapten-specific IFN-γ-producing CD8+ effectors in skin draining lymph nodes (dLNs) and their massive recruitment into the allergen-exposed skin. Adoptive transfer and antibody depletion experiments as well as in vitro studies revealed that iNKT cells (1) reduce the severity of CHS, even in presensitized mice, (2) require hapten presentation by CD1d+ dendritic cells (DCs) to dampen skin inflammation, and (3) produce IL-4 and IL-13 after CD1d-dependent in vitro stimulation by hapten-loaded DCs only in the presence of IFN-γ released from activated CD8+ effector T cells. In corollary, mice double deficient in IL-4 and IL-13 exhibit an exacerbated CHS. Finally, iNKT-suppressive function is independent of Foxp3+ regulatory T cells (Tregs). These data highlight that, besides Foxp3+ Tregs, iNKT cells are potent downregulators of CD8+ T cell–mediated CHS, and underscore that both cell types are important for the regulation of allergic skin inflammation

Etude par spectroscopie de photoelectrons (XPS) et radiochimie (C136) de l'interaction des ions chlorures avec le film passif forme sur le nickel

SIGLEINIST T 76594 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Relation microstructure-propriétés mécaniques d'un acier martensitique inoxydable

The relationship between microstructure and mechanical properties of MaX (1.4006) martensitic stainless steel has been studied. Optical microscopy was used to characterize the microstructure and the volume fraction of retained ferrite was measured by image analysis. Mechanical properties were measured in uni-axial tensile testing and a composite model has been developed to capture the effect of both the retained ferrite and the carbon content of the martensitic phase. First results show a reasonable correlation between the experimental stress-strain curves and the model. Results are discussed in view of a previous study on plain martensitic carbon steels

Les fonctions innées des lymphocytes T CD8 dans la lutte contre le cancer

International audienceno abstrac

Identification des effecteurs de l'immunosurveillance au cours de la leucémie myéloïde chronique (du patient à la modélisation chez l'animal)

POITIERS-BU Médecine pharmacie (861942103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Allotransplantation Is Associated With Exacerbation of CD8 T-Cell Senescence: The Particular Place of the Innate CD8 T-Cell Component

International audienceImmunosenescence is a physiological process that is associated with changes in the immune system, particularly among CD8 T-cells. Recent studies have hypothesized that senescent CD8 T-cells are produced with chronologic age by chronic stimulation, leading to the acquisition of hallmarks of innate-like T-cells. While conventional CD8 T-cells are quite well characterized, CD8 T-cells sharing features of NK cells and memory CD8 T-cells, are a newly described immune cell population. They can be distinguished from conventional CD8 T-cells by their combined expression of panKIR/NKG2A and Eomesodermin (E), a unique phenotype closely associated with IFN-γ production in response to innate stimulation. Here, we first provided new evidence in favor of the innate character of panKIR/NKG2A(+) E(+) CD8 T-cells in normal subjects, documenting their position at an intermediate level in the innateness gradient in terms of both innate IFN-γ production and diminished mitochondrial mass. We also revealed that CD8 E(+) panKIR/NKG2A(+) T-cells, hereafter referred to as Innate E(+) CD8 T-cells, exhibit increased senescent (CD27(-) CD28(-)) phenotype, compared to their conventional memory counterparts. Surprisingly, this phenomenon was not dependent on age. Given that inflammation related to chronic viral infection is known to induce NK-like marker expression and a senescence phenotype among CD8 T-cells, we hypothesized that innate E(+) CD8 T-cells will be preferentially associated with exacerbated cellular senescence in response to chronic alloantigen exposure or CMV infection. Accordingly, in a pilot cohort of stable kidney allotransplant recipients, we observed an increased frequency of the Innate E(+) CD8 T-cell subset, together with an exacerbated senescent phenotype. Importantly, this phenotype cannot be explained by age alone, in clear contrast to their conventional memory counterparts. The senescent phenotype in CD8 T-cells was further increased in cytomegalovirus (CMV) positive serology transplant recipients, suggesting that transplantation and CMV, rather than aging by itself, may promote an exacerbated senescent phenotype of innate CD8 T-cells. In conclusion, we proposed that kidney transplantation, via the setting of inflammatory stimuli of alloantigen exposure and CMV infection, may exogenously age the CD8 T-cell compartment, especially its innate component. The physiopathological consequences of this change in the immune system remain to be elucidated

Innate T-αβ lymphocytes as new immunological components of anti-tumoral "off-target" effects of the tyrosine kinase inhibitor dasatinib

International audienceKinase inhibitors hold great potential as targeted therapy against malignant cells. Among them, the tyrosine kinase inhibitor dasatinib is known for a number of clinically relevant off-target actions, attributed in part to effects on components of the immune system, especially conventional T-cells and natural killer (NK)-cells. Here, we have hypothesized that dasatinib also influences non-conventional T-αβ cell subsets known for their potential anti-tumoral properties, namely iNKT cells and the distinct new innate CD8 T-cell subset. In mice, where the two subsets were originally characterized, an activated state of iNKT cells associated with a shift toward an iNKT cell Th1-phenotype was observed after dasatinib treatment in vivo. Despite decreased frequency of the total memory CD8 T-cell compartment, the proportion of innate-memory CD8 T-cells and their IFNγ expression in response to an innate-like stimulation increased in response to dasatinib. Lastly, in patients administered with dasatinib for the treatment of BCR-ABL-positive leukemias, we provided the proof of concept that the kinase inhibitor also influences the two innate T-cell subsets in humans, as attested by their increased frequency in the peripheral blood. These data highlight the potential immunostimulatory capacity of dasatinib on innate T-αβ cells, thereby opening new opportunities for chemoimmunotherapy