The purpose of this study was to determine the effect of dendritic cell (DC) transfers on the incidence of diabetes in female nonobese diabetic (NOD) mice. Groups of 4-wk-old NOD female mice were given a single foot pad of DCs (70-90% purity) isolated from the draining lymph nodes (LN) of the pancreas (PLN), the cervical LNs, or the axillary/inguinal LNs. In addition, other groups of NOD mice received purified spleen DCs, purified PLN T cells (the major contaminating population in DC preparations), or the injection vehicle PBS. All groups were monitored for diabetes for one year.Significant protection from diabetes was observed in NOD mice receiving > 1 x 104 PLN DCs in comparison to mice receiving other DCs populations, PLN T cells, or PBS (P < 0.05). The pancreata of NOD mice that received PLN DCs demonstrated significantly lower levels of lymphocytic infiltration in the islets that age-sex matched nondiabetic female NOD control mice (P < 0.05). LN cells from nondiabetic NOD mice that received PLN DC protected irradiated female recipients from the adoptive transfer of diabetes to a greater degree than LN cells from age and sex matched nondiabetic female NOD mice that did not receive PLN DC transfers at 36 d (P = 0.014) and at 1 yr (P = 0.0015) after transfer.These data suggest that the PLN DC transfers are able to modulate autoimmunity and limit diabetes expression in the NOD mouse. PLN DCs transfers may regulate autoimmunity by the induction of regulatory cells. (J. Clin. Invest. 1992.
and adenosine cause frequent side effects as a result of nonspecific adenosine receptor stimulation. Selective agonism of the adenosine A 2A receptor should result in a similar degree of coronary vasodilation (and thus similar perfusion images) with fewer side effects. Methods and Results-In a multicenter, randomized, single-blind, 2-arm crossover trial, 240 patients underwent 2 single photon emission computed tomographic (SPECT) imaging studies in random order, first after pharmacological stress with adenosine and a second study with the selective adenosine A 2A receptor agonist binodenoson, using 1 of 4 dosing regimens. Safety, tolerability, and SPECT image concordance between the 2 agents were examined. Exact categorical agreement in the extent and severity of reversible perfusion defects ranged from 79% to 87%, with kappa values from 0.69 to 0.85, indicating very good to excellent agreement between binodenoson and adenosine. The risk of any safety event/side effect was significantly lower with any dose of binodenoson than with adenosine (PՅ0.01) because of a dose-related reduction in subjective side effects, as objective events were infrequent. There was a reduction in the severity of chest pain, dyspnea, and flushing in all binodenoson doses compared with adenosine (PϽ0.01), and the magnitude of severity reduction was dose-related.
Conclusions-The
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