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Notably, previously reported dose-dependent changes in tenocyte bioactivity to soluble IGF-1 within the CG scaffold were replicated by using a single dose of soluble IGF-1 in scaffolds containing increasingly sulfated GAGs.
In the latter study, CD4+ T cells deficient for SAP, and therefore limited in their ability to interact with B cells, still adopted a Tfh phenotype when a second dose of soluble antigen was given 72 hr later.
The animals gavaged with ten-fold higher dose of soluble OVA (0.5 mg OVA/CpG + MP) showed a strong trend towards increased anti-OVA antibody production relative to the saline control group but the data were not statistically significant.
Similarly, studies from other groups have shown that usually a much higher dose of soluble HER2/neu protein is required to induce detectable T-cell immunity [ 13- 15, 17, 45].
Compared with the group that received a combination of radiosurgery and soluble tissue factor but without phosphatidylserine, the animal survival rate was significantly higher in mice that received a combination of radiosurgery and a low dose of soluble tissue factor and phosphatidylserine (P < 0.01).
Compared with the group that received coadministration of soluble tissue factor and phosphatidylserine but without radiosurgery, the animal survival rates were significantly higher in mice that received a combination of radiosurgery and a low dose of soluble tissue factor and phosphatidylserine or a combination of radiosurgery and soluble tissue factor (P < 0.001).
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However, strategies to induce durable tolerance using high doses of soluble antigen have to date been unsuccessful, due to lack of efficacy and the risk of hypersensitivity.
Low dose tolerance is induced upon injection of sub-immunogenic doses of soluble antigens and therapeutical efficacy has been demonstrated even with sub-nanomolar doses of antigens [37].
The results of the present study demonstrate the capability of our model to explain the dynamics of differentiation marker expression in response to variable doses of soluble inducing factors as well as the regeneration of cell populations from subpopulations.
This was in agreement with the results of cell-based and in vitro binding assays showing that only higher doses of soluble heparin suppressed the angiogenic properties of HUVECs and interactions of VEGF-A and related molecules more efficiently than the ocular fluid.
Titrated doses of soluble or immobilized control IgG1 or elotuzumab mAb were added to the wells.
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