135 research outputs found
Speech-generating devices: effectiveness of interface design—a comparative study of autism spectrum disorders
Fast learning in free-foraging bumble bees is negatively correlated with lifetime resource collection
Migration of Th1 Lymphocytes Is Regulated by CD152 (CTLA-4)-Mediated Signaling via PI3 Kinase-Dependent Akt Activation
Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response
Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110δ prevents chronic rejection of heart allografts.
Chronic rejection is the major cause of long-term heart allograft failure, characterized by tissue infiltration by recipient T cells with indirect allospecificity. Phosphoinositol-3-kinase p110δ is a key mediator of T cell receptor signaling, regulating both T cell activation and migration of primed T cells to non-lymphoid antigen-rich tissue. We investigated the effect of genetic or pharmacologic inactivation of PI3K p110δ on the development of chronic allograft rejection in a murine model in which HY-mismatched male hearts were transplanted into female recipients. We show that suppression of p110δ activity significantly attenuates the development of chronic rejection of heart grafts in the absence of any additional immunosuppressive treatment by impairing the localization of antigen-specific T cells to the grafts, while not inducing specific T cell tolerance. p110δ pharmacologic inactivation is effective when initiated after transplantation. Targeting p110δ activity might be a viable strategy for the treatment of heart chronic rejection in humans
Neural circuitry at age 6Â months associated with later repetitive behavior and sensory responsiveness in autism
Adapted design of multimedia-facilitated language learning program for children with autism
Mechanisms of T cell organotropism
F.M.M.-B. is supported by the British Heart Foundation, the Medical Research Council of the UK and the Gates Foundation
What am I doing in Timbuktu: person-environment picture recognition for persons with intellectual disability
Efficacy of entecavir and tenofovir in chronic hepatitis B under treatment in the public health system in southern Brazil
Benefits of the use of ICT in school activities by students with motor, speech, visual, and hearing impairment: A literature review
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