A combination of soluble helper factors bypasses the requirement for stimulator cells and induces nonspecific cytotoxic T cell responses

The specificity of cytotoxic T lymphocyte (CTL) responses generated in the presence of lymphokines was studied. Thymic responder cells were activated in the presence of stimulator cells that differed in their metabolic activity. After 5 days of culture, the cytotoxic response was estimated in a 4-h 51Cr-release test. Coculture of thymic responders with irradiated splenic stimulator cells in the presence of interleukin 2(IL 2) led to preferential cytolysis of target cells that expressed the same histocompatibility antigens as the cells used for sensitization. Addition of T cell cytotoxicity-inducing factor 1 (TCF1), however, to those cultures made the presence of stimulator cells unnecessary and induced cytotoxic responses against all target cells tested, including target cells syngeneic to the responder cells. This activation was neither due to contaminating mitogen nor to the effect of heterologous serum in the assay system. The conclusion of these findings was that either polyclonal activation of CTL was induced by TCF1 or that some specific CTL clones differentiated into unrestricted killer cells under the influence of TCF1

Capacity of different cell types to stimulate cytotoxic T lymphocyte precursor cells in the presence of interleukin 2

Plastic-adherent cells enriched for dendritic cells (AC) were found to be among the most potent stimulator cells for the activation of cytotoxic T lymphocytes (CTL) in vitro in the presence of interleukin 2 (IL 2) and a constant second set of allogeneic stimulator cells. Concanavalin A-activated nylon wool-nonadherent spleen cells ( CNWT ), concanavalin A-activated unfractionated spleen cells ( Cspl ), and some variants of the ESb T lymphoma line were equally effective as stimulator cells, however, and provoked a substantial cytotoxic response at concentrations of 10(4) cells per culture or less. In contrast, nonactivated nylon wool-nonadherent spleen cells ( NWT ) or unfractionated spleen cells (Spl) and cells of the P815 mastocytoma, the Meth A fibrosarcoma, and the T cell lymphomas Ly 5178 Eb and ESb did not stimulate cytotoxic responses at these cell concentrations. The strong stimulatory potential of the Cspl preparation was reduced by treatment with anti-Thy-1 antibody plus complement, whereas the stimulatory activity of the AC preparation was resistant to this treatment. All cell types tested expressed class I major histocompatibility antigens. Nonactivated NWT cells, in contrast to the CNWT preparation, showed no detectable staining with anti-I-E or anti-I-A antibodies and also a slightly weaker staining with class I antisera. Experiments with the tumor cell lines revealed, however, that there was no strict correlation between stimulatory potential and density of class I alloantigens or the expression of I-E determinants. Experiments on primary cytotoxic responses in vivo gave similar results. Experiments in cultures with a single set of stimulator cells and I region-compatible responder cells indicated that AC and Cspl or CNWT also have a markedly stronger capacity than NWT to induce IL 2-dependent DNA synthesis

Induction of IL 2 receptor expression and cytotoxicity of thymocytes by stimulation with TCF1

We investigated the role of T cell cytotoxicity inducing factor 1 (TCF1) in the induction of a cytotoxic T cell response. We found that help-deficient thymocyte cultures supplied with saturating amounts of purified IL 2 did not develop CTL in a 5-day culture. The expression of cytotoxicity was dependent on the addition of TCF1 derived from the T cell hybridoma K15. TCF1 also induced proliferation of thymocytes in the presence of IL 2. Only the PNA- thymocyte subpopulation responded to TCF1 with proliferation and cytotoxicity in the presence of IL 2. The monokine IL 1 also induced proliferation in this subpopulation but failed to induce cytotoxicity. IL 1 was further distinguished from TCF1 by inhibition of IL 1-induced but not TCF1-induced proliferation by anti-IL 1 antibodies. In addition, using anti-IL 2 receptor antibodies (AMT 13), we showed that TCF1 in the presence of IL 2 substantially increased IL 2 receptor expression in thymocytes. IL 1 had the same effect on induction of IL 2 receptor expression as TCF1. Because some effects of IL 1 and TCF1 are distinct and some overlap, we discuss whether IL 1 and TCF1 induce different subsets of PNA- thymocytes

Amoebozoa possess lineage-specific globin gene repertoires gained by individual horizontal gene transfers

The Amoebozoa represent a clade of unicellular amoeboid organisms that display a wide variety of lifestyles, including free-living and parasitic species. For example, the social amoeba Dictyostelium discoideum has the ability to aggregate into a multicellular fruiting body upon starvation, while the pathogenic amoeba Entamoeba histolytica is a parasite of humans. Globins are small heme proteins that are present in almost all extant organisms. Although several genomes of amoebozoan species have been sequenced, little is known about the phyletic distribution of globin genes within this phylum. Only two flavohemoglobins (FHbs) of D. discoideum have been reported and characterized previously while the genomes of Entamoeba species are apparently devoid of globin genes. We investigated eleven amoebozoan species for the presence of globin genes by genomic and phylogenetic in silico analyses. Additional FHb genes were identified in the genomes of four social amoebas and the true slime mold Physarum polycephalum. Moreover, a single-domain globin (SDFgb) of Hartmannella vermiformis, as well as two truncated hemoglobins (trHbs) of Acanthamoeba castellanii were identified. Phylogenetic evidence suggests that these globin genes were independently acquired via horizontal gene transfer from some ancestral bacteria. Furthermore, the phylogenetic tree of amoebozoan FHbs indicates that they do not share a common ancestry and that a transfer of FHbs from bacteria to amoeba occurred multiple times

The large longitudinal spread of solar energetic particles during the January 17, 2010 solar event

We investigate multi-spacecraft observations of the January 17, 2010 solar energetic particle event. Energetic electrons and protons have been observed over a remarkable large longitudinal range at the two STEREO spacecraft and SOHO suggesting a longitudinal spread of nearly 360 degrees at 1AU. The flaring active region, which was on the backside of the Sun as seen from Earth, was separated by more than 100 degrees in longitude from the magnetic footpoints of each of the three spacecraft. The event is characterized by strongly delayed energetic particle onsets with respect to the flare and only small or no anisotropies in the intensity measurements at all three locations. The presence of a coronal shock is evidenced by the observation of a type II radio burst from the Earth and STEREO B. In order to describe the observations in terms of particle transport in the interplanetary medium, including perpendicular diffusion, a 1D model describing the propagation along a magnetic field line (model 1) (Dr\"oge, 2003) and the 3D propagation model (model 2) by (Dr\"oge et al., 2010) including perpendicular diffusion in the interplanetary medium have been applied, respectively. While both models are capable of reproducing the observations, model 1 requires injection functions at the Sun of several hours. Model 2, which includes lateral transport in the solar wind, reveals high values for the ratio of perpendicular to parallel diffusion. Because we do not find evidence for unusual long injection functions at the Sun we favor a scenario with strong perpendicular transport in the interplanetary medium as explanation for the observations.Comment: The final publication is available at http://www.springerlink.co

Drift-induced deceleration of Solar Energetic Particles

We investigate the deceleration of Solar Energetic Particles (SEPs) during their propagation from the Sun through interplanetary space, in the presence of weak to strong scattering in a Parker spiral configuration, using relativistic full orbit test particle simulations. The calculations retain all three spatial variables describing particles’ trajectories, allowing to model any transport across the magnetic field. Large energy change is shown to occur for protons, due to the combined effect of standard adiabatic deceleration and a significant contribution from particle drift in the direction opposite to that of the solar wind electric field. The latter drift-induced deceleration is found to have a stronger effect for SEP energies than for galactic cosmic rays. The kinetic energy of protons injected at 1 MeV is found to be reduced by between 35 and 90% after four days, and for protons injected at 100 MeV by between 20 and 55%. The overall degree of deceleration is a weak function of the scattering mean free path, showing that, although adiabatic deceleration plays a role, a large contribution is due to particle drift. Current SEP transport models are found to account for drift-induced deceleration in an approximate way and their accuracy will need to be assessed in future work

Transport Modeling of Interplanetary Electrons in the 2002 October 20 Solar Particle Event

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