Wideband-tuneable, nanotube mode-locked, fibre laser

Ultrashort-pulse lasers with spectral tuning capability have widespread applications in fields such as spectroscopy, biomedical research and telecommunications1–3. Mode-locked fibre lasers are convenient and powerful sources of ultrashort pulses4, and the inclusion of a broadband saturable absorber as a passive optical switch inside the laser cavity may offer tuneability over a range of wavelengths5. Semiconductor saturable absorber mirrors are widely used in fibre lasers4–6, but their operating range is typically limited to a few tens of nanometres7,8, and their fabrication can be challenging in the 1.3–1.5 mm wavelength region used for optical communications9,10. Single-walled carbon nanotubes are excellent saturable absorbers because of their subpicosecond recovery time, low saturation intensity, polarization insensitivity, and mechanical and environmental robustness11–16. Here, we engineer a nanotube–polycarbonate film with a wide bandwidth (>300 nm) around 1.55 mm, and then use it to demonstrate a 2.4 ps Er31-doped fibre laser that is tuneable from 1,518 to 1,558 nm. In principle, different diameters and chiralities of nanotubes could be combined to enable compact, mode-locked fibre lasers that are tuneable over a much broader range of wavelengths than other systems

Cell-to-Cell Interactions and Signals Involved in the Reconstitution of Peripheral CD8+ TCM and TEM Cell Pools

We here describe novel aspects of CD8+ and CD4+ T cell subset interactions that may be clinically relevant and provide new tools for regulating the reconstitution of the peripheral CD8+ T cell pools in immune-deficient states. We show that the reconstitution capacity of transferred isolated naïve CD8+ T cells and their differentiation of effector functions is limited, but both dramatically increase upon the co-transfer of CD4+ T cells. This helper effect is complex and determined by multiple factors. It was directly correlated to the number of helper cells, required the continuous presence of the CD4+ T cells, dependent on host antigen-presenting cells (APCs) expressing CD40 and on the formation of CD4/CD8/APC cell clusters. By comparing the recovery of (CD44+CD62Lhigh) TCM and (CD44+CD62Llow) TEM CD8+ T cells, we found that the accumulation of TCM and TEM subsets is differentially regulated. TCM-cell accumulation depended mainly on type I interferons, interleukin (IL)-6, and IL-15, but was independent of CD4+ T-cell help. In contrast, TEM-cell expansion was mainly determined by CD4+ T-cell help and dependent on the expression of IL-2Rβ by CD8 cells, on IL-2 produced by CD4+ T-cells, on IL-15 and to a minor extent on IL-6

An Alternate STAT6-Independent Pathway Promotes Eosinophil Influx into Blood during Allergic Airway Inflammation

Enhanced eosinophil responses have critical roles in the development of allergic diseases. IL-5 regulates the maturation, migration and survival of eosinophils, and IL-5 and eotaxins mediate the trafficking and activation of eosinophils in inflamed tissues. CD4⁺ Th2 cells are the main producers of IL-5 and other cells such as NK also release this cytokine. Although multiple signalling pathways may be involved, STAT6 critically regulates the differentiation and cytokine production of Th2 cells and the expression of eotaxins. Nevertheless, the mechanisms that mediate different parts of the eosinophilic inflammatory process in different tissues in allergic airway diseases remain unclear. Furthermore, the mechanisms at play may vary depending on the context of inflammation and microenvironment of the involved tissues. We employed a model of allergic airway disease in wild type and STAT6-deficient mice to explore the roles of STAT6 and IL-5 in the development of eosinophilic inflammation in this context. Quantitative PCR and ELISA were used to examine IL-5, eotaxins levels in serum and lungs. Eosinophils in lung, peripheral blood and bone marrow were characterized by morphological properties. CD4⁺ T cell and NK cells were identified by flow cytometry. Antibodies were used to deplete CD4⁺ and NK cells. We showed that STAT6 is indispensible for eosinophilic lung inflammation and the induction of eotaxin-1 and -2 during allergic airway inflammation. In the absence of these chemokines eosinophils are not attracted into lung and accumulate in peripheral blood. We also demonstrate the existence of an alternate STAT6-independent pathway of IL-5 production by CD4⁺ and NK cells that mediates the development of eosinophils in bone marrow and their subsequent movement into the circulation

Inducible deletion of CD28 prior to secondary nippostrongylus brasiliensis infection impairs worm expulsion and recall of protective memory CD4 (+) T cell responses

IL-13 driven Th2 immunity is indispensable for host protection against infection with the gastrointestinal nematode Nippostronglus brasiliensis. Disruption of CD28 mediated costimulation impairs development of adequate Th2 immunity, showing an importance for CD28 during the initiation of an immune response against this pathogen. In this study, we used global CD28−/− mice and a recently established mouse model that allows for inducible deletion of the cd28 gene by oral administration of tamoxifen (CD28−/loxCre+/−+TM) to resolve the controversy surrounding the requirement of CD28 costimulation for recall of protective memory responses against pathogenic infections. Following primary infection with N. brasiliensis, CD28−/− mice had delayed expulsion of adult worms in the small intestine compared to wild-type C57BL/6 mice that cleared the infection by day 9 post-infection. Delayed expulsion was associated with reduced production of IL-13 and reduced serum levels of antigen specific IgG1 and total IgE. Interestingly, abrogation of CD28 costimulation in CD28−/loxCre+/− mice by oral administration of tamoxifen prior to secondary infection with N. brasiliensis resulted in impaired worm expulsion, similarly to infected CD28−/− mice. This was associated with reduced production of the Th2 cytokines IL-13 and IL-4, diminished serum titres of antigen specific IgG1 and total IgE and a reduced CXCR5+ TFH cell population. Furthermore, total number of CD4+ T cells and B220+ B cells secreting Th1 and Th2 cytokines were significantly reduced in CD28−/− mice and tamoxifen treated CD28−/loxCre+/− mice compared to C57BL/6 mice. Importantly, interfering with CD28 costimulatory signalling before re-infection impaired the recruitment and/or expansion of central and effector memory CD4+ T cells and follicular B cells to the draining lymph node of tamoxifen treated CD28−/loxCre+/− mice. Therefore, it can be concluded that CD28 costimulation is essential for conferring host protection during secondary N. brasiliensis infection