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- Watanabe, M., et al.
(författare)
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Ex Vivo Generation of Donor Antigen-Specific Immunomodulatory Cells A Comparison Study of Anti-CD80/86 mAbs and CTLA4-lg Costimulatory Blockade
- 2018
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Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 27:11, s. 1692-1704
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Tidskriftsartikel (refereegranskat)abstract
- Adoptive transfer of alloantigen-specific immunomodulatory cells generated ex vivo with anti-CD80/CD86 mAbs (2D10.4/IT2.2) holds promise for operational tolerance after transplantation. However, good manufacturing practice is required to allow widespread clinical application. Belatacept, a clinically approved cytotoxic T-lymphocyte antigen 4-immunoglobulin that also binds CD80/CD86, could be an alternative agent for 2D10.4/IT2.2. With the goal of generating an optimal cell treatment with clinically approved reagents, we evaluated the donor-specific immunomodulatory effects of belatacept- and 2D10.4/IT2.2-generated immunomodulatory cells. Immunomodulatory cells were generated by coculturing responder human peripheral blood mononuclear cells (PBMCs) (50 x 10(6) cells) with irradiated donor PBMCs (20 x 10(6) cells) from eight human leukocyte antigen-mismatched responder-donor pairs in the presence of either 2D10.4/IT2.2 (3 mu g/10(6) cells) or belatacept (40 mu g/10(6) cells). After 14 days of coculture, the frequencies of CD4(+) T cells, CD8(+) T cells, and natural killer cells as well as interferon gamma (IFN-gamma) production in the 2D10.4/IT2.2- and belatacept-treated groups were lower than those in the control group. The percentage of CD19(+) B cells was higher in the 2D10.4/IT2.2- and belatacept-treated groups than in the control group. The frequency of CD4(+)CD25(+)CD127(low)FOXP3(+) T cells increased from 4.1 +/- 1.0% (preculture) to 7.1 +/- 2.6% and 7.3 +/- 2.6% (day 14) in the 2D10.4/IT2.2- and belatacept-treated groups, respectively (p<0.05). Concurrently, delta-2 FOXP3 mRNA expression increased significantly. Compared with cells derived from the no-antibody treated control group, cells generated from both the 2D10.4/IT2.2- and belatacept-treated groups produced lower IFN-gamma and higher interleukin-10 levels in response to donor-antigens, as detected by enzyme-linked immunospot. Most importantly, 2D10.4/IT2.2- and belatacept-generated cells effectively impeded the proliferative responses of freshly isolated responder PBMCs against donor-antigens. Our results indicate that belatacept-generated donor-specific immunomodulatory cells possess comparable phenotypes and immunomodulatory efficacies to those generated with 2D10.4/IT2.2. We suggest that belatacept could be used for ex vivo generation of clinical grade alloantigen-specific immunomodulatory cells for tolerance induction after transplantation.
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- Ayerden, N.P., et al.
(författare)
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Design, fabrication and characterization of LVOF-based IR microspectrometers
- 2014
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9781628410785 ; 9130
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Konferensbidrag (refereegranskat)abstract
- This paper presents the design, fabrication and characterization of a linear variable optical filter (LVOF) that operates in the infrared (IR) spectral range. An LVOF-based microspectrometer is a tapered-cavity Fabry-Perot optical filter placed on top of a linear array of detectors. The filter transforms the optical spectrum into a lateral intensity profile, which is recorded by the detectors. The IR LVOF has been fabricated in an IC-compatible process flow using a resist reflow and is followed by the transfer etching of this resist pattern into the optical resonator layer. This technique provides the possibility to fabricate a small, robust and high-resolution micro-spectrometer in the IR spectral range directly on a detector chip. In these designs, the LVOF uses thin-film layers of sputtered Si and SiO 2 as the high and low refractive index materials respectively. By tuning the deposition conditions and analyzing the optical properties with a commercial ellipsometer, the refractive index for Si and SiO2 thin-films was measured and optimized for the intended spectral range. Two LVOF microspectrometers, one operating in the 1.8-2.8 μm, and the other in the 3.0-4.5 μm wavelength range, have been designed and fabricated on a silicon wafer. The filters consist of a Fabry-Perot structure combined with a band-pass filter to block the out-of-band transmission. Finally, the filters were fully characterized with an FTIR spectrometer and the transmission curve widening was investigated. The measured transmittance curves were in agreement with theory. The characterization shows a spectral resolution of 35-60 nm for the short wavelength range LVOF and 70 nm for the long wavelength range LVOF, which can be further improved using signal processing algorithms.
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- Brinkfeldt, Klas, et al.
(författare)
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Microshutters for MEMS-based time-of-flight measurements in space
- 2011
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Ingår i: Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS). - 1084-6999. - 9781424496327 ; , s. 597-600
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Konferensbidrag (refereegranskat)abstract
- This paper reports on the fabrication, integration and first operation of a mechanical microshutter in a time-of-flight (TOF) based ion detector in space. The microshutter is fabricated from a silicon on insulator (SOI) wafer and operated in a resonance mode, 306 kHz. Open time of the shutter is 100 ns. The microshutters are integrated in the PRIMA instrument, which is part of the payload on the Swedish PRISMA mission. PRISMA was successfully launched into low Earth orbit on June 15, 2010.
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- Campbell, TM, et al.
(författare)
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Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency
- 2022
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 219:7
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients’ fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2–specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity.
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