Adoptive immunotherapy with functional T cells is potentially an effective therapeutic strategy for combating many types of cancer and viral infection. However, exhaustion of antigen-specific T cells represents a major challenge to this type of approach. In an effort to overcome this problem, we reprogrammed clonally expanded antigen-specific CD8(+) T cells from an HIV-1-infected patient to pluripotency. The T cell-derived induced pluripotent stem cells were then redifferentiated into CD8(+) T cells that had a high proliferative capacity and elongated telomeres. These "rejuvenated" cells possessed antigen-specific killing activity and exhibited T cell receptor gene-rearrangement patterns identical to those of the original T cell clone from the patient. We also found that this method can be effective for generating specific T cells for other pathology-associated antigens. Thus, this type of approach may have broad applications in the field of adoptive immunotherapy.
Two water-soluble, silver(I) complexes showing a wide spectrum of effective antibacterial and antifungal activities, i.e., ([Ag(Hhis)].0.2EtOH)2 (1; H2his = L-histidine) and [Ag(Hpyrrld)]2 (3; H2pyrrld = (S)-(-)-2-pyrrolidone-5-carboxylic acid) were prepared. In aqueous solution 1 and 3 were present as dimers, whereas in the solid state they were polymers. Crystallization of 1 by slow evaporation and/or vapor diffusion gave water-insoluble crystals of [Ag(Hhis)]n (2) showing modest antimicrobial activities. The complex 1 in the solid state is a polymer formed by intermolecular hydrogen-bonding interactions between dimeric [Ag(Hhis)]2 cores, while 2 is a different polymer without a core complex. X-ray crystallography revealed that 2 was a left-handed helical polymer consisting of a bent, 2-coordinate silver(I) atom bonding to the Namino atom of one Hhis- ligand and the N pi atom of a different Hhis- ligand. Of particular note is the fact that Ocarboxyl atoms do not participate in the coordination. X-ray crystallography also revealed that 3 was a left-handed helical polymer formed by self-assembly of dimeric [Ag(Hpyrrld)]2 cores with an intramolecular metal(I)-metal(I) interaction (Ag-Ag distance, 2.9022(7) A). The FT-IR and the solid-state 13C and 15N NMR spectra showed that the dimeric core of 1 was formed through Ag-N bonds, while that of 3 was formed through Ag-O bonds. The molecular ions of 1 and 3 were detected by the positive-ion electrospray ionization (ESI) mass spectrometry. For 1-3, characterization by elemental analysis, TG/DTA, FT-IR, and variable-temperature solid-state 13C NMR and room-temperature 15N NMR measurements was performed, and for 1 and 3, that by solution molecular weight measurements and solution (109Ag, 1H, and 13C) NMR spectroscopies was also carried out. The antibacterial and antifungal activities of 1 and 3 were remarkable and comparable to those of the previous silver(I)-N-heterocycle complexes.
It was recently discovered that sputter deposition of metal onto the surface of an ionic liquid generates nanoparticles in the liquid with no additional stabilizing agents. We performed small-angle X-ray scattering (SAXS) experiments to investigate the temperature effect on the structure and formation process of Au nanoparticles synthesized by this method. We selected 1-buthyl-3-methylimidazolium tetrafluoroborate as the capture ionic liquid and obtained SAXS intensities of the nanoparticles generated at various temperatures from 20 to 80 °C. The SAXS results revealed that the particle size was relatively uniform for a fixed temperature, and that it strongly depended on the temperature of the capture ionic liquid. Temperature change causes drastic changes in the viscosity of the liquid and the diffusive velocities of the scattered Au particles. Therefore, it is concluded that the collision frequency of the Au particles is one of the important factors in determining their size, as well as the stabilization effect for once generated nanoparticles by the constituent ions of the ionic liquid. The ions work to prevent further particle-aggregation in balance with the collision frequency of particles. Most sputtered Au particles are Au atoms in our experimental condition, and the formation of the nanoparticles occurs in the beginning of dispersion in the ionic liquid.
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