Juergen Schmitz

Nomenclature of monocytes and dendritic cells in blood

Monocytes and cells of the dendritic cell lineage circulate in blood and eventually migrate into tissue where they further mature and serve various functions, most notably in immune defense. Over recent years these cells have been characterized in detail with the use of cell surface markers and flow cytometry, and subpopulations have been described. The present document proposes a nomenclature for these cells and defines 3 types of monocytes (classical, intermediate, and nonclassical monocytes) and 3 types of dendritic cells (plasmacytoid and 2 types of myeloid dendritic cells) in human and in mouse blood. This classification has been approved by the Nomenclature Committee of the International Union of Immunological Societies, and we are convinced that it will facilitate communication among experts and in the wider scientific community.

Functional dichotomy of plasmacytoid dendritic cells: Antigen‐specific activation of T cells versus production of type I interferon

Human plasmacytoid dendritic cells (PDC) are believed to link innate and adaptive immunity by producing type I interferon (IFN‐I) and triggering adaptive T cell‐mediated immunity. However, it remains elusive to which degree both PDC functions are linked. Here we show that CMV antigen targeted to PDC using a CD303 (blood dendritic cell antigen 2, BDCA‐2) mAb is rapidly endocytosed and traffics via early sorting endosomes to emerging MHC‐enriched compartments. Both processes occur independently of TLR ligand stimulation. Restimulation of CMV‐specific CD4+ effector‐memory T helper cells by autologous PDC and induction of IFN‐I production in PDC are dependent on appropriate stimulation. Type B CpG oligonucleotide (CpG‐B)‐stimulated PDC efficiently process and present CMV antigen and are thus capable of stimulating CMV‐specific effector‐memory T helper cells. CpG‐A‐stimulated PDC produce large amounts of IFN‐I and express programmed death receptor‐1 ligand 1. CpG‐A plus CpG‐B‐co‐stimulated PDC behave like CpG‐B‐stimulated PDC, suggesting that antigen processing and presentation in PDC is dependent on stimulation that concurrently inhibits IFN‐I production. In vivo targeting of antigens to PDC via CD303 combined with appropriate PDC stimulation may allow induction of specific T cell activation.

Optoelectronic properties of photodiodes for the mid-and far-infrared based on the InAs/GaSb/AlSb materials family

The optoelectronic properties of short-period InAs/(GaIn)Sb superlattices (SLs) grown by molecular beam epitaxy on GaSb substrates are discussed. We report on the optimization of the SL materials properties with special emphasis on the use for infrared detection devices. The materials quality is evaluated by using high resolution x-ray diffraction, atomic force microscopy, and photoluminescence spectroscopy. In- plane magneto-transport investigations were performed applying mobility spectrum analysis. The SL diodes were analyzed performing standard electro-optical measurements. The observation of resonances in the I-V curves in the regime of Zener-tunneling due to Wannier-Stark localization opens a new tool for the electrical investigation of photodiodes with low band gap energy. The status of the processing technology is reported demonstrating the feasibility for the fabrication of 256 X 256 focal plane arrays operating in the 8-to-12 micrometers atmospheric window. In addition, results are given for mid-infrared SL-diodes, grown with lattice matched AlGaAsSb barriers instead in the binary InAs/GaSb SL system.

Trap centers and minority carrier lifetimes in InAs/(GaIn)Sb superlattice long wavelength photodetectors

Trap centers and minority carrier lifetimes are investigated in InAs/(GaIn)Sb superlattices used for photodetectors in the far-infrared wavelength range. In our InAs/(GaIn)Sb superlattice photodiodes, trap centers located at an energy level of ~1/3 band gap below the effective conduction band edge could be identified by simulating the current-voltage characteristics of the diodes. The simulation includes diffusion currents, generation-recombination contributions, band-to-band coherent tunneling, and trap assisted tunneling. By including the contributions due to trap-assisted tunneling, excellent reproduction of the current voltage curves is possible for diodes with cut-off wavelength in the whole 8-32 μm spectral range at temperatures between 140 K and 25 K. The model is supported by the observation of defect-related optical transitions at ~2/3 of the band-to-band energy in the spectra of the low temperature electroluminescence of the devices. With the combination of Hall- and photoconductivity measurements, minority carrier lifetimes are extracted as a dependence of temperature and carrier density.

Enhanced Dendritic Cell-Induced Immune Responses Mediated by the Novel C-Type Lectin Receptor mDCAR1

The dendritic cell (DC) immunoreceptors (DCIR) and DC-immunoactivating receptors (DCAR) represent a subfamily of cell surface C-type lectin receptors (CLR), whose multifunctional capacities range from classical Ag uptake and immunoregulatory mechanisms to the involvement in DC ontogeny. On the basis of the generation of specific mAbs, we functionally characterized mouse DCAR1 (mDCAR1) as a member of the DCIR/DCAR family. Expression of mDCAR1 was strongly tissue dependent. mDCAR1 expression on DCs was restricted to the CD8+ DC subset in spleen and thymus and on subpopulations of CD11b+ myeloid cells in bone marrow and spleen, whereas the molecule was not detectable on both cell types in lymph nodes and peripheral blood. With respect to the function of CLRs as pattern recognition receptors, Ag delivered via mDCAR1 was internalized, was trafficked to early and late endosomes/lysosomes and, as a consequence, induced cellular and humoral responses in vivo even in the absence of CD40 stimulation. Intriguingly, upon triggering mDCAR1, CD8+ DCs increased the secretion of bioactive IL-12, whereas IL-10 release is markedly reduced, thereby indicating that Ag recognized by mDCAR1 induces enhanced proinflammatory responses. These data indicate that mDCAR1 is a functional receptor on cells of the immune system and provides further insights into the regulation of immune responses by CLRs.

CD45RA-expressing memory/effector Th cells committed to production of interferon-γ lack expression of CD31

It has been considered before that human naive and memory/effector CD4+ T-cells cannot be subdivided solely according to the differential expression of CD45 isoforms. By the lack of expression of CD31 we have identified a subset of CD4+ CD45RA+ CD31- cells which show distinct features of antigen-experienced Th1 cells. Short term stimulation of highly purified human peripheral blood CD4+ T-cells with PMA/ionomycin, followed by the cytometric analysis of intracellular cytokines, showed that a minor subpopulation of CD4+ CD45RA+ CD45RO- cells is able to produce interferon-gamma (IFN-gamma) rapidly, a characteristic of antigen-experienced Th1 cells. Whereas among CD45RA+ CD4+ T-cells both CD31+ and CD31- subsets produce interleukin-2 (IL-2) upon PMA/ionomycin stimulation, only the CD31- subpopulation is able to produce IFN-gamma. Thus, our phenotypic and functional characterization of CD45RA+ CD45RO- Th cells shows that CD45RA+ CD45RO- cells do not represent a homogeneous population of antigen-unexperienced, naive T-cells. We speculate that a certain subset of human CD4+, CD45RO+ memory T-cells reverts to expression of the CD45RA isoform, and that this subset can be identified by the lack of CD31 expression.

InAs/Ga1-xInxSb infrared superlattice diodes: correlation between surface morphology and electrical performance

The structural properties of InAs/Ga1-xInxSb infrared (IR) superlattice layers grown by MBE on GaSb substrates have been investigated using high-resolution X- ray diffraction, atomic force microscopy (AFM), secondary ion mass spectroscopy and photoluminescence (PL) spectroscopy. Excellent layers could be grown with a residual mismatch below 1 X 10-3 showing interference oscillations in the X-ray diffraction pattern and high PL efficiency. IR-photodiodes processed from such layers show high responsivity and low leakage currents. The influence of n- and p-doping on the PL efficiency of IR superlattices has been investigated, showing a stronger decrease of the PL intensity for n-doping than for p-doping. Growing the IR-SLs with an As/In V/III ratio below 5, defects with a size of about 1 to 5 micrometers in diameter are observed in the AFM scans. The surface morphology between the defects remains perfect. The defects do not significantly affect the X-ray diffraction patterns and the PL intensity. In a minority-carrier-device, such as IR- photodiodes, the defects are associated with defect-assisted tunneling currents leading to a strong degradation of the electrical performance. By optimizing the growth conditions the defect density can be significantly reduced resulting in a surface roughness given by the standard deviation of the measured height profile of the AFM measurement below 0.3 nm leading to excellent device performance.

Impact of polysialylated CD56 on natural killer cell cytotoxicity

BackgroundSiglec-7, a sialic acid binding inhibitory receptor expressed by NK cells is masked in vivo by a so far unknown ligand. It shows a strong binding prevalence for α-2,8-linked disialic acids in vitro.ResultsHere we describe the expression of PSA-NCAM (α-2,8-linked polysialic acid modified NCAM) on functional adult peripheral blood natural killer cells and examine its possible role in masking Siglec-7. Unmasking of Siglec-7 using Clostridium perfringens neuraminidase massively reduces NK cell cytotoxicity. By contrast a specific removal of PSA using Endo-NF does not lead to a reduction of NK cell cytotoxicity.ConclusionThe results presented here therefore indicate that PSA-NCAM is not involved in masking Siglec-7.

Physics and applications of III-Sb-based type-I QW diode lasers

We present recent progress achieved in the development of type-I GaInAsSb/AlGaAsSb quantum-well (QW) lasers covering the 1.74-2.34micrometers spectral range. Diode lasers based on the broadened waveguide design comprising 3 Qws have been studied in detail. Laser structures emitting at 2.23 micrometers exhibited a record high internal quantum efficiency of 89%, internal loss of 6.8cm-1, and threshold current density at infinite cavity length as low as 120 A/cm2, indicating the superior quality of these devices. For the 2micrometers lasers a high characteristic temperature of 179K for the threshold current was achieved for temperatures between 250 and 280 K. In order to investigate the heterobarrier leakage associated with thermally activated carriers, laser structures emitting at 2.23micrometers with different Al- concentrations in the barriers and separate confinement regions have been studied. While the structure with 40% Al revealed the highest To of 103K, the laser with 20% Al yielded the best power efficiency, with a maximum value of 30%. 1.7W in cw mode at room temperature has been achieved for broad area single emitters at (lambda) =2 micrometers , with high-reflection/antireflection coated mirror facets, mounted epi-side down. As an application, tunable diode lasers absorption spectroscopy (TDLAS) sensing small concentrations of methane has been demonstrated using our 2.3micrometers diode laser.