These CTLs (notably CD8(+) T cells) recognize and kill insulin-secreting pancreatic

beta cells, reducing their number PD0325901 purchase by similar to 90%. The resulting reduction of insulin secretion causes the defective regulation of glucose metabolism, leading to the characteristic symptoms of diabetes. Recognition of beta cells as targets by CTLs depends on the interactions between MHC-peptide complexes on the surface of beta cells and receptors (TCRs) on T cells. Those CTLs with high affinity TCRs (also called high avidity T cells) cause most of the harm, while those with low affinity TCRs (also called low avidity T cells) play a more mysterious role. Recent experimental evidence suggests that low avidity T cells accumulate as memory T cells during the disease and may be protective in NOD mice (a strain prone to developing T1D), delaying disease progression. It has been hypothesized that such low avidity T cells afford disease protection either by crowding the islets of Langerhans, where beta cells reside, or by killing antigen presenting cells (APCs).

In this paper, we explore the hypothesized mechanisms for

this protective effect in the context of a series of models for (1) the interactions of low and high avidity T cells, (2) the effect of APCs and (3) the feedback from beta cell killing to autoantigen-induced T cell proliferation. We analyze properties of these models, noting consistency of predictions with observed behaviour. We then use the this website models to examine the influence of various treatment strategies on the progression of the Mannose-binding protein-associated serine protease disease. The model reveals that progressive accumulation of memory low avidity

autoreactive T cells during disease progression makes treatments aimed at expanding these protective T cell types more effective close to, or at the onset of clinical disease. It also provides evidence for the hypothesis that low avidity T cells kill APCs (rather than the alternate hypothesis that they crowd the islets). Crown Copyright (C) 2008 Published by Elsevier Ltd. All rights reserved.”
“Research in songbirds shows that singing behavior is regulated by both brain areas involved in vocal behavior as well as those involved in social behavior. Interestingly, the precise role of these regions in song can vary as a function of the social, environmental and breeding context. To date, little is known about the neurotransmitters underlying such context-dependent regulation of song. Dopamine (DA) modulates highly motivated, goal-directed behaviors (including sexually motivated song) and emerging data implicate DA in the context-dependent regulation of singing behavior. This study was performed to begin to examine whether differences in DA receptors may underlie, in part, context-dependent differences in song production.