IL-2 Mediates CD4+ T Cell Help in the Breakdown of Memory-Like CD8+ T Cell Tolerance under Lymphopenic Conditions

Background: Lymphopenia results in the proliferation and differentiation of naïve T cells into memory-like cells in the apparent absence of antigenic stimulation. This response, at least in part due to a greater availability of cytokines, is thought to promote anti-self responses. Although potentially autoreactive memory-like CD8 + T cells generated in a lymphopenic environment are subject to the mechanisms of peripheral tolerance, they can induce autoimmunity in the presence of antigen-specific memory-like CD4 + T helper cells. Methodology/Principal Findings: Here, we studied the mechanisms underlying CD4 help under lymphopenic conditions in transgenic mice expressing a model antigen in the beta cells of the pancreas. Surprisingly, we found that the self-reactivity mediated by the cooperation of memory-like CD8 + and CD4 + T cells was not abrogated by CD40L blockade. In contrast, treatment with anti-IL-2 antibodies inhibited the onset of autoimmunity. IL-2 neutralization prevented the CD4-mediated differentiation of memory-like CD8 + T cells into pathogenic effectors in response to self-antigen cross-presentation. Furthermore, in the absence of helper cells, induction of IL-2 signaling by an IL-2 immune complex was sufficient to promote memory-like CD8 + T cell self-reactivity. Conclusions/Significance: IL-2 mediates the cooperation of memory-like CD4 + and CD8 + T cells in the breakdown of crosstolerance, resulting in effector cytotoxic T lymphocyte differentiation and the induction of autoimmune disease

Optimized XUV source at 100 kHz repetition rate

Fiber based laser systems at high repetition rate are becoming very attractive for high-order harmonics generation as they allow to reach high intensities. Their characteristics (central wavelength, energy and pulse duration) require specific optimizing conditions. We analyse how the harmonic efficiency with such a system is influenced by several parameters (atomic gas media, pressure, interaction geometry (a jet or a cell)). This study allows us to define optimal conditions for HHG appropriate to this new type of laser and experimentally, a photon flux higher than 1012 photons/s is measured

Collection and spectral control of high-order harmonics generated with a 50 W high-repetition rate Ytterbium femtosecond laser system

We generate high-order harmonics with a 50 W, Yb femtosecond fiber laser system operating at 100 kHz in a tight focusing configuration. We achieve a high photon flux even with pulses longer than 500 fs. We collect the diverging extreme ultraviolet (XUV) harmonic beam in a 35 mrad wide solid angle by using a spectrometer designed to handle the high thermal load under vacuum and refocus the XUV beam onto a detector where the beam is characterised or can alternatively be used for experiments. This setup is designed for a 50 eV XUV bandwidth and offers the possibility to perform XUV-IR pump probe experiments with both temporal and spectral resolution. The high-order harmonics were generated and optimized at 100 kHz by using several gas target geometries (a gas jet and a semi-infinite gas cell) and several gases (argon, krypton, xenon) that provide XUV beams with different characteristics. After the spectrometer and for high-order harmonic generation (HHG) in xenon, we detect more than 4×10 10 photons per second over four harmonics, that is a useful XUV power on target of 0.1 μW. This corresponds to the emission of more than 1 μW per harmonic at the source and we achieved a similar flux with both the semi-infinite cell and the jet. In addition, we observe a strong spectral selectivity when generating harmonics in a semi-infinite gas cell as few harmonics clearly dominate the neighbouring harmonics. We attribute this spectral selectivity to phase matching effects

Génération d'harmoniques d'ordre élevé en régime de forte focalisation à 100 kHz

De nombreuses applications nécessitent des sources XUV à haut taux de répétition avec un important nombre de photons XUV par impulsion. Potentiellement ces sources peuvent être obtenues par génération d'harmoniques d'ordre élevé avec un laser fondamental à haute cadence. Cependant, la faible énergie et la longue durée des impulsions délivrées par ces systèmes laser exigent de focaliser fortement le faisceau fondamental afin d'atteindre des éclairements adéquats pour la génération d'harmoniques (∼ 1014 W/cm2). Ceci s'avère généralement défavorable pour l'efficacité du processus qu'il convient d'optimiser. Dans ce travail, une étude numérique permet de définir des conditions générales d'optimisation de la génération d'harmoniques en forte focalisation et nous observons la signature d'un accord de phase parfait. Ces conditions sont reproduites expérimentalement et nous obtenons une optimisation de l'émission harmonique avec un nombre de photons XUV (harmoniques d'ordres 15-17 et 19) émis dans du Xe supérieur à 1012 s−1 à la cadence de 100 kHz

Dissipative Soliton Generation and Amplification in Erbium-Doped Fibers Operating at 1.55 mu m

WOS:000349119600029International audienceWe report on our recent developments on ultrafast pulse generation in erbium-doped fiber laser systems operating in the 1550 nm wavelength range. This work concerns the generation of ultrafast pulses from dissipative soliton fiber lasers featuring resonant saturable absorber mirrors as well as their amplification in highly efficient erbium-doped large-mode-area fibers. Different amplification schemes featuring all-fiber components are studied leading to the achievement of record pulse energy from a high repetition rate laser system. The system delivers 8 W of average power at 35 MHz repetition rate corresponding to 230 nJ pulse energy. After external compression, near transform-limited, 850 fs-long pulses are obtained. The pulse peak power exceeds 180 kW