322 research outputs found
TLR2-Dependent Induction of IL-10 and Foxp3+CD25+CD4+ Regulatory T Cells Prevents Effective Anti-Tumor Immunity Induced by Pam2 Lipopeptides In Vivo
16 S-[2,3-bis(palmitoyl)propyl]cysteine (Pam2) lipopeptides act as toll-like receptor (TLR)2/6 ligands and activate natural killer (NK) cells and dendritic cells (DCs) to produce inflammatory cytokines and cytotoxic NK activity in vitro. However, in this study, we found that systemic injection of Pam2 lipopeptides was not effective for the suppression of NK-sensitive B16 melanomas in vivo. When we investigated the immune suppressive mechanisms, systemic injection of Pam2 lipopeptides induced IL-10 in a TLR2-dependent manner. The Pam2 lipopeptides increased the frequencies of Foxp3+CD4+ regulatory T (T reg) cells in a TLR2- and IL-10- dependent manner. The T reg cells from Pam2-lipopeptide injected mice maintained suppressor activity. Pam2 lipopeptides, plus the depletion of T reg with an anti-CD25 monoclonal antibody, improved tumor growth compared with Pam2 lipopeptides alone. In conclusion, our data suggested that systemic treatment of Pam2 lipopeptides promoted IL-10 production and T reg function, which suppressed the effective induction of anti-tumor immunity in vivo. It is necessary to develop an adjuvant that does not promote IL-10 and T reg function in vivo for the future establishment of an anti-cancer vaccine
An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors.
Hematopoietic stem cells (HSCs) are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Through this system, we have identified hemopexin (HPX) and interleukin-1α as responsible for HSC maintenance in vitro. Subsequent molecular analysis revealed that HPX reduces intracellular reactive oxygen species levels within cultured HSCs. Furthermore, bone marrow immunostaining and 3D immunohistochemistry revealed that HPX is expressed in non-myelinating Schwann cells, known HSC niche constituents. These results highlight the utility of this fully defined all-recombinant protein-based culture system for reproducible in vitro HSC culture and its potential to contribute to the identification of factors responsible for in vitro maintenance, expansion, and differentiation of stem cell populations
Synergistic Formation of Radicals by Irradiation with Both Vacuum Ultraviolet and Atomic Hydrogen: A Real-Time In Situ Electron Spin Resonance Study
We report on the surface modification of polytetrafluoroethylene (PTFE) as an
example of soft- and bio-materials that occur under plasma discharge by
kinetics analysis of radical formation using in situ real-time electron spin
resonance (ESR) measurements. During irradiation with hydrogen plasma,
simultaneous measurements of the gas-phase ESR signals of atomic hydrogen and
the carbon dangling bond (C-DB) on PTFE were performed. Dynamic changes of the
C-DB density were observed in real time, where the rate of density change was
accelerated during initial irradiation and then became constant over time. It
is noteworthy that C-DBs were formed synergistically by irradiation with both
vacuum ultraviolet (VUV) and atomic hydrogen. The in situ real-time ESR
technique is useful to elucidate synergistic roles during plasma surface
modification.Comment: 14 pages, 4 figure
A new scheme for the running coupling constant in gauge theories using Wilson loops
We propose a new renormalization scheme of the running coupling constant in
general gauge theories using the Wilson loops. The renormalized coupling
constant is obtained from the Creutz ratio in lattice simulations and the
corresponding perturbative coefficient at the leading order. The latter can be
calculated by adopting the zeta-function resummation techniques. We perform a
benchmark test of our scheme in quenched QCD with the plaquette gauge action.
The running of the coupling constant is determined by applying the step-scaling
procedure. Using several methods to improve the statistical accuracy, we show
that the running coupling constant can be determined in a wide range of energy
scales with relatively small number of gauge configurations.Comment: 30pages, figs and comments added,reference added(v3
- …