1,25(OH)2D3 Promotes the Efficacy of CD28 Costimulation Blockade by Abatacept.

Inhibition of the CD28:CD80/CD86 T cell costimulatory pathway has emerged as an effective strategy for the treatment of T cell-mediated inflammatory diseases. However, patient responses to CD28-ligand blockade by abatacept (CTLA-4-Ig) in conditions such as rheumatoid arthritis are variable and often suboptimal. In this study, we show that the extent to which abatacept suppresses T cell activation is influenced by the strength of TCR stimulation, with high-strength TCR stimulation being associated with relative abatacept insensitivity.

Vitamin D Antagonises the Suppressive Effect of Inflammatory Cytokines on CTLA-4 Expression and Regulatory Function.

The immune suppressive protein CTLA-4 is constitutively expressed by Tregs and induced in effector T cells upon activation. Its crucial role in adaptive immunity is apparent from the fatal autoimmune pathology seen in CTLA-4 knockout mice. However, little is known regarding factors that regulate CTLA-4 expression and their effect upon its function to remove CD80 and CD86 from antigen presenting cells by transendocytosis.

Flexible emotion-based decision-making behavior varies in current and former smokers.

Introduction: Suboptimal decision-making is a feature in the initiation and maintenance of substance use, often manifested in choosing for short-term benefits rather than long-term gain, and the failure to display cognitive flexibility, respectively. Studies of nicotine users typically focus on characterizing those who are already addicted; less is known about decision-making in former smokers.

Methods: Non- (n=21), former daily- (n=23) and current daily smokers (n=24), completed the contingency-shifting variant Iowa Gambling Task (csIGT), in which the reward and punishment contingencies of the decks are systematically varied after 100 trials of the 'standard' IGT.

Availability of 25-hydroxyvitamin D(3) to APCs controls the balance between regulatory and inflammatory T cell responses.

1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], the active form of vitamin D, exerts potent effects on several tissues including cells of the immune system, where it affects T cell activation, differentiation and migration. The circulating, inactive form of vitamin D, 25(OH)D(3), is generally used as an indication of vitamin D status. However, use of this precursor depends on its uptake by cells and subsequent conversion by the enzyme 25(OH)D(3)-1α-hydroxylase (CYP27B1) into active 1,25(OH)(2)D(3).

Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model.

Background: Gut microbes influence animal health and thus, are potential targets for interventions that slow aging. Live E. coli provides the nematode worm Caenorhabditis elegans with vital micronutrients, such as folates that cannot be synthesized by animals.

Constitutive clathrin-mediated endocytosis of CTLA-4 persists during T cell activation.

CTLA-4 is one of the most important negative regulators of the T cell immune response. However, the subcellular distribution of CTLA-4 is unusual for a receptor that interacts with cell surface transmembrane ligands in that CTLA-4 is rapidly internalized from the plasma membrane. It has been proposed that T cell activation can lead to stabilization of CTLA-4 expression at the cell surface.

Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis.