Mapping the Solar Wind from its Source Region into the Outer Corona

Knowledge of the radial variation of the plasma conditions in the coronal source region of the solar wind is essential to exploring coronal heating and solar wind acceleration mechanisms. The goal of the present proposal is to determine as many plasma parameters in that region as possible by coordinating different observational techniques, such as Interplanetary Scintillation Observations, spectral line intensity observations, polarization brightness measurements and X-ray observations. The inferred plasma parameters are then used to constrain solar wind models

Interpretation of Solar Wind Ion Composition Measurements from Ulysses

The ion compositions measured in situ in the solar wind are important since the ion fractions carry information on the plasma conditions in the inner corona. The conditions in the inner corona define the properties of the solar wind plasma flow. Thus, if the ion fraction measurements can be used to unravel some of the plasma parameters in the inner corona, they will provide a valuable contribution to solving the heating and acceleration problem of the solar wind. The ion charge states in the solar wind carry information on electron temperature, electron density and ion flow speed. They are also sensitive to the shape of the electron distribution function. Through carefully modeling the solar wind and calculating the ion fractions predicted for different solar wind conditions, constraints on the electron temperature and ion flow speeds can be placed if the electron density is measured using polarization brightness measurements

Interpretation of Solar Wind Composition Measurements from Ulysses

Ion charge states measured in situ in interplanetary space carry information on the properties of the solar wind plasma in the inner corona. This information is, however, not easy to extract from the in situ observations. The goal of the proposal was to determine solar wind models and coronal observations that are necessary tools for the interpretation of charge state observations. It has been shown that the interpretation of the in situ ion fractions are heavily dependent on the assumptions about conditions in the inner corona

Solar wind Acceleration from the Upper Chromosphere to the Corona in Coronal Hole Regions

The dynamic behavior of the plasma in the chromosphere/transition region /inner corona is vital for the acceleration of the solar wind. With new theoretical descriptions of the solar atmosphere and corona, and the increased observational possibilities provided by the SOHO spacecraft, it is possible to conduct an integrated study of the solar atmosphere and corona using observational and theoretical approaches. Over the past few years a series of observational techniques have been used to estimate the solar wind densities, temperatures and flow speed in the inner corona. These estimates suggest that the solar wind has higher outflow speeds in the inner corona and lower densities than previously assumed. A comparison with densities derived from atmospheric models support these lower densities

Mapping the Solar Wind from its Source Region into the Outer Corona

Knowledge of the radial variation of the plasma conditions in the coronal source region of the solar wind is essential to exploring coronal heating and solar wind acceleration mechanisms. The goal of the proposal was to determine as many plasma parameters in the solar wind acceleration region and beyond as possible by coordinating different observational techniques, such as Interplanetary Scintillation Observations, spectral line intensity observations, polarization brightness measurements and X-ray observations. The inferred plasma parameters were then used to constrain solar wind models

Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation

Background: Reconstitution of cytomegalovirus-specific CD3+CD8+ T cells (CMV-CTLs) after allogeneic hematopoietic stem cell transplantation (HSCT) is necessary to bring cytomegalovirus (CMV) reactivation under control. However, the parameters determining protective CMV-CTL reconstitution remain unclear to date. Design and Methods: In a prospective tri-center study, CMV-CTL reconstitution was analyzed in the peripheral blood from 278 patients during the year following HSCT using 7 commercially available tetrameric HLA-CMV epitope complexes. All patients included could be monitored with at least CMV-specific tetramer. Results: CMV-CTL reconstitution was detected in 198 patients (71%) after allogeneic HSCT. Most importantly, reconstitution with 1 CMV-CTL per µl blood between day +50 and day +75 post-HSCT discriminated between patients with and without CMV reactivation in the R+/D+ patient group, independent of the CMV-epitope recognized. In addition, CMV-CTLs expanded more daramtaically in patients experiencing only one CMV-reactivation than those without or those with multiple CMV reactivations. Monitoring using at least 2 tetramers was possible in 63% (n = 176) of the patients. The combinations of particular HLA molecules influenced the numbers of CMV-CTLs detected. The highest CMV-CTL count obtained for an individual tetramer also changed over time in 11% of these patients (n = 19) resulting in higher levels of HLA-B*0801 (IE-1) recognizing CMV-CTLs in 14 patients. Conclusions: Our results indicate that 1 CMV-CTL per µl blood between day +50 to +75 marks the beginning of an immune response against CMV in the R+/D+ group. Detection of CMV-CTL expansion thereafter indicates successful resolution of the CMV reactivation. Thus, sequential monitoring of CMV-CTL reconstitution can be used to predict patients at risk for recurrent CMV reactivation

Functionality and Cell Senescence of CD4/ CD8-Selected CD20 CAR T Cells Manufactured Using the Automated CliniMACS Prodigy® Platform

Clinical studies using autologous CAR T cells have achieved spectacular remissions in refractory CD19+ B cell leukaemia, however some of the patient treatments with CAR T cells failed. Beside the heterogeneity of leukaemia, the distribution and senescence of the autologous cells from heavily pretreated patients might be further reasons for this. We performed six consecutive large-scale manufacturing processes for CD20 CAR T cells from healthy donor leukapheresis using the automated CliniMACS Prodigy® platform. Starting with a CD4/CD8-positive selection, a high purity of a median of 97% T cells with a median 65-fold cell expansion was achieved. Interestingly, the transduction rate was significantly higher for CD4+ compared to CD8+ T cells and reached in a median of 23%. CD20 CAR T cells showed a good specific IFN-γ secretion after cocultivation with CD20+ target cells which correlated with good cytotoxic activity. Most importantly, 3 out of 5 CAR T cell products showed an increase in telomere length during the manufacturing process, while telomere length remained consistent in one and decreased in another process. In conclusion, this shows for the first time that beside heterogeneity among healthy donors, CAR T cell products also differ regarding cell senescence, even for cells manufactured in a standardised automated process

IL-2 Stimulated but Not Unstimulated NK Cells Induce Selective Disappearance of Peripheral Blood Cells: Concomitant Results to a Phase I/II Study

In an ongoing clinical phase I/II study, 16 pediatric patients suffering from high risk leukemia/tumors received highly purified donor natural killer (NK) cell immunotherapy (NK-DLI) at day (+3) +40 and +100 post haploidentical stem cell transplantation. However, literature about the influence of NK-DLI on recipient's immune system is scarce. Here we present concomitant results of a noninvasive in vivo monitoring approach of recipient's peripheral blood (PB) cells after transfer of either unstimulated (NK-DLI(unstim)) or IL-2 (1000 U/ml, 9–14 days) activated NK cells (NK-DLI(IL-2 stim)) along with their ex vivo secreted cytokine/chemokines. We performed phenotypical and functional characterizations of the NK-DLIs, detailed flow cytometric analyses of various PB cells and comprehensive cytokine/chemokine arrays before and after NK-DLI. Patients of both groups were comparable with regard to remission status, immune reconstitution, donor chimerism, KIR mismatching, stem cell and NK-DLI dose. Only after NK-DLI(IL-2 stim) was a rapid, almost complete loss of CD56(bright)CD16(dim/−) immune regulatory and CD56(dim)CD16(+) cytotoxic NK cells, monocytes, dendritic cells and eosinophils from PB circulation seen 10 min after infusion, while neutrophils significantly increased. The reduction of NK cells was due to both, a decrease in patients' own CD69(−) NCR(low)CD62L(+) NK cells as well as to a diminishing of the transferred cells from the NK-DLI(IL-2 stim) with the CD56(bright)CD16(+/−)CD69(+)NCR(high)CD62L(−) phenotype. All cell counts recovered within the next 24 h. Transfer of NK-DLI(IL-2 stim) translated into significantly increased levels of various cytokines/chemokines (i.e. IFN-γ, IL-6, MIP-1β) in patients' PB. Those remained stable for at least 1 h, presumably leading to endothelial activation, leukocyte adhesion and/or extravasation. In contrast, NK-DLI(unstim) did not cause any of the observed effects. In conclusion, we assume that the adoptive transfer of NK-DLI(IL-2 stim) under the influence of ex vivo and in vivo secreted cytokines/chemokines may promote NK cell trafficking and therefore might enhance efficacy of immunotherapy