Induction of specific tolerance by intrathymic injection of recipient muscle cells transfected with donor class I major histocompatibility complex.

Induction of tolerance to allogeneic MHC antigens has been a goal in the field of transplantation because it would reduce or eliminate the need for generalized immunosuppression. Although encouraging results have been obtained in experimental models by exposing recipient thymus to donor cells before transplantation, donor cells are not typically available at that time, and the donor antigens responsible for the effect are poorly defined. In the present study, thymic tolerance was demonstrated without using donor cells. Recipient thymus was injected before transplantation with autologous myoblasts and myotubes that were genetically modified to express allogeneic donor-type MHC class I antigen. Donor-specific unresponsiveness was induced to a completely MHC-disparate liver transplant and to a subsequent donor-type cardiac allograft, but not a third-party allograft. In vitro, recipient CTL demonstrated a 10-fold reduction in killing of donor cells, but not of third-party cells. Our results demonstrate: (1) that recipient muscle cells can be genetically engineered to induce donor-specific unresponsiveness when given intrathymically, and (2) transfected recipient cells expressing only donor MHC class I antigen can induce tolerance to a fully allogeneic donor

Immunity to MHC class I antigen after direct DNA transfer into skeletal muscle.

Plasmid cDNA encoding the alpha-chain of either membrane-bound (pcRT.45) or secreted (pcRQ.B3) RT1Aa MHC class I Ag were transferred to Lewis (RT1(1)) rat skeletal muscle by direct injection. Rats were challenged 7 days later with an ACI (RT1a) heterotropic heart transplant, and cardiac allograft survival, RT1Aa-specific antibody levels, and frequency of ACI-specific CTL were monitored. Graft rejection was accelerated by > or = 2 days in an Ag-specific and dose-dependent manner in pcRT.45-injected rats. The pcRQ.B3-injected rats also rejected grafts more rapidly; however, graft rejection was accelerated by only 1 day, and graft infiltrates were less pronounced than in pcRT.45-injected rats. Injection of pcRT.45 resulted in an increase in ACI-specific CTL precursor frequency 3 days post-transplant, whereas there was no significant change in rats pretreated with pcRQ.B3 injection. Compared with rats injected with a control plasmid encoding firefly luciferase, transfer of pcRT.45 resulted in an increase in RT1Aa-specific IgG and IgM antibody 3 days after heart transplantation. Transfer of pcRQ.B3 resulted in a similar mean increase in RT1Aa-specific IgG and IgM antibody after transplantation, but the variability from rat to rat was greater, with some animals exhibiting strong priming, and others showing little or no priming by gene injection. Our results suggest that skeletal muscle can express either membrane-bound or secreted MHC class I Ag after gene transfer, but that the membrane-bound form is more immunogenic than the secreted form in the high responder Lewis rat. Direct DNA transfer to skeletal muscle provides a rapid and specific approach to studying immunity to allogeneic MHC Ag

Use of donor serum to prevent passive transfer of hyperacute rejection

Organ transplantation in presensitized recipients continues to be contraindicated for heart and kidney recipients due to the risk of hyperacute rejection, which has no known treatment at this time. We tested whether donor serum, which contains soluble MHC class I antigen, is able to neutralize the effect of anti-donor antibody in the recipient and prevent hyperacute or accelerated rejection. A rat model of passive immunization was used to test the role of anti-donor antibody in hyperacute rejection. Seven of 10 recipients of hyperimmune serum (HyS), derived from Lewis rats (RT1l) following 3 ACI (RT1a) skin grafts, developed hyperacute or accelerated rejection. Intravenous injection of ACI serum prior to the HyS administration prevented hyperacute rejection in all recipients tested. When third-party (Wistar-Furth, RT1u) serum was given to Lewis rats injected with HyS, hyperacute rejection was not abrogated. When examining the mechanism of this effect, a simple antibody blocking phenomenon was found to be unlikely since flow cytometry analysis showed that ACI serum needed to be present at > or = 256-fold excess compared to HyS to block anti-ACI antibody binding to RT1.Aa+cells by 50%. We tested whether the RT1.Aa class I antigen in ACI serum had other biologic properties that resulted in the prolonged graft survival. However, removal of RT1.Aa antigen from ACI serum prior to use in the passive transfer model did not abrogate the graft prolongation observed previously. These data suggest that components of donor serum other than MHC class I antigen may be useful for preventing the antibody-mediated component of hyperacute rejection

Single fiber laser based wavelength tunable excitation for CRS spectroscopy

We demonstrate coherent Raman spectroscopy (CRS) using a tunable excitation source based on a single femtosecond fiber laser. The frequency difference between the pump and the Stokes pulses was generated by soliton self-frequency shifting (SSFS) in a nonlinear optical fiber. Spectra of C-H stretches of cyclohexane were measured simultaneously by stimulated Raman gain (SRG) and coherent anti-Stokes Raman scattering (CARS) and compared. We demonstrate the use of spectral focusing through pulse chirping to improve CRS spectral resolution. We analyze the impact of pulse stretching on the reduction of power efficiency for CARS and SRG. Due to chromatic dispersion in the fiber-optic system, the differential pulse delay is a function of Stokes wavelength. This differential delay has to be accounted for when performing spectroscopy in which the Stokes wavelength needs to be scanned. CARS and SRG signals were collected and displayed in two dimensions as a function of both the time delay between chirped pulses and the Stokes wavelength, and we demonstrate how to find the stimulated Raman spectrum from the two-dimensional plots. Strategies of system optimization consideration are discussed in terms of practical applications

Eocene Podocarpium (Leguminosae) from South China and its biogeographic implications

Podocarpium A. Braun ex Stizenberger is one of the most common legumes in the Neogene of Eurasia, including fossil fruits, seeds, leaves, and possible flower and pollen grains. This genus is not completely consistent with any extant genera according to gross morphological characters and poorly preserved cuticular structures reported in previous studies. The fossil pods collected from the coal-bearing series of the Changchang Basin of Hainan Island and Maoming Basin of Guangdong, South China, are examined by morphologically comparative work, with special reference to venation patterns and placental position. These distinctive features, as well as the ovule development of pods from different growing stages and the epidermal structure of the pods, as distinguished from previous records lead to the conclusion that these fossils can be recognized as a new species of Podocarpium, P. eocenicum sp. nov. This new discovery indicates that Podocarpium had arrived in South China by the Eocene. Investigation on the fossil records of this extinct genus shows that P. eocenicum is the earliest and lowest latitude fossil data. The possible occurrence pattern of this genus is revealed as follows: Podocarpium had distributed in the South China at least in the middle Eocene, and then migrated to Europe during the Oligocene; in the Miocene this genus reached its peak in Eurasia, spreading extensively across subtropical areas to warm temperate areas; finally, Podocarpium shrank rapidly and became extinct in Eurasia during the Pliocene

Consensus of self-driven agents with avoidance of collisions

In recent years, many efforts have been addressed on collision avoidance of collectively moving agents. In this paper, we propose a modified version of the Vicsek model with adaptive speed, which can guarantee the absence of collisions. However, this strategy leads to an aggregated state with slowly moving agents. We therefore further introduce a certain repulsion, which results in both faster consensus and longer safe distance among agents, and thus provides a powerful mechanism for collective motions in biological and technological multi-agent systems.Comment: 8 figures, and 7 page