Search results for "priming"

Beta-Catenin mediates tumor-induced immunosuppression by inhibiting cross-priming of CD8(+) T cells

2014

Tumors activate -catenin in DCs to suppress CD8 immunity by inhibiting cross-priming; -catenin-suppressed CD8 immunity could be rescued by enhancing cross-priming. Whereas CD8(+) T cells are essential for anti-tumor immunity, tumors often evade CD8(+) T cell surveillance by immunosuppression. As the initiators of antigen-specific immune responses, DCs are likely to play a central role in regulating the balance between immunity and tolerance to tumor antigens and are specialized in their ability to cross-present exogenous tumor antigens on MHC class I molecules to initiate CD8(+) T cell immunity. However, it remains unclear whether and how tumors modulate DC functions to suppress CD8(+) T ce…

CD4 blockade directly inhibits mouse and human CD4+ T cell functions independent of Foxp3+ Tregs

2013

CD4(+) helper T cells orchestrate protective immunity against pathogens, yet can also induce undesired pathologies including allergies, transplant rejection and autoimmunity. Non-depleting CD4-specific antibodies such as clone YTS177.9 were found to promote long-lasting T cell tolerance in animal models. Thus, CD4 blockade could represent a promising therapeutic approach for human autoimmune diseases. However, the mechanisms underlying anti-CD4-induced tolerance are incompletely resolved. Particularly, multiple immune cells express CD4 including Foxp3(+) regulatory T cells (Tregs) and dendritic cells (DCs), both controlling the activation of CD4(+)Foxp3(-) helper T cells. Utilizing mixed le…

Liver-primed memory T cells generated under noninflammatory conditions provide anti-infectious immunity.

2013

SummaryDevelopment of CD8+ T cell (CTL) immunity or tolerance is linked to the conditions during T cell priming. Dendritic cells (DCs) matured during inflammation generate effector/memory T cells, whereas immature DCs cause T cell deletion/anergy. We identify a third outcome of T cell priming in absence of inflammation enabled by cross-presenting liver sinusoidal endothelial cells. Such priming generated memory T cells that were spared from deletion by immature DCs. Similar to central memory T cells, liver-primed T cells differentiated into effector CTLs upon antigen re-encounter on matured DCs even after prolonged absence of antigen. Their reactivation required combinatorial signaling thro…

Efficient homologous prime-boost strategies for T cell vaccination based on virus-like particles.

2005

Induction of high frequencies of specific T cells by vaccination requires prime-boost regimens. To reach optimal immune responses, it is necessary to use different vectors for priming and boosting as e.g. DNA vaccination followed by boosting with a recombinant viral vector. Here, we show that vaccines based on virus-like particles (VLP) displaying peptide epitopes are equally effective to induce CTL responses if used in a homologous or heterologous prime-boost setting. Strikingly, high frequencies (>20% of CD8(+) cells) of protective CTL could be induced and maintained by weekly injection of VLP. Thus, the use of VLP may avoid the requirement for complicated heterologous prime-boost regi…

LFA-1 activity state on dendritic cells regulates contact duration with T cells and promotes T-cell priming.

2010

AbstractA key event in the successful induction of adaptive immune responses is the antigen-specific activation of T cells by dendritic cells (DCs). Although LFA-1 (lymphocyte function–associated antigen 1) on T cells is considered to be important for antigen-specific T-cell activation, the role for LFA-1 on DCs remains elusive. Using 2 different approaches to activate LFA-1 on DCs, either by deletion of the αL-integrin cytoplasmic GFFKR sequence or by silencing cytohesin-1–interacting protein, we now provide evidence that DCs are able to make use of active LFA-1 and can thereby control the contact duration with naive T cells. Enhanced duration of DC/T-cell interaction correlates inversely …

Priming with a combination of proangiogenic growth factors improves wound healing in normoglycemic mice

2011

Growth factors and/or angiogenic factors are supposed to improve wound healing. The aim of our study was to evaluate the effects of subcutaneous pretreatment with combinatory proangiogenic factors on wound closure, mechan - ical properties, vessel density and morphology. Twenty-eight Balb/c mice were divided equally into two groups. A mixture of VEGF (35.0 µg), bFGF (2.5 µg) and P dGF (3.5 µg) was administered subcutaneously 3, 5 and 7 days to 14 mice before full thickness skin punch biopsy wounding, whereas 14 control animals received three injections of 0.2 ml saline solution. Wound sizes were assessed daily and the repaired tissues were harvested 7 days after complete wound closure. Comp…

Priming with a Combination of Proangiogenic Growth Factors Enhances Wound Healing in Streptozotocin-Induced Diabetes in Mice

2010

<i>Background:</i> Numerous proangiogenic growth factors have been shown to improve impaired wound healing. This study evaluated the effects of subcutaneous pretreatment with a combination of proangiogenic growth factors on wound closure, mechanical properties, vessel density, and morphology. <i>Methods:</i> Thirty-six Balb/c mice with streptozotocin-induced diabetes were divided into 3 groups. A mixture of VEGF (35.0 µg), bFGF (2.5 µg), and PDGF (3.5 µg) was administered subcutaneously 3, 5, and 7 days prior to wounding in the first group, whereas the second group received three doses of 3.5 µg PDGF. Wound sizes were assessed daily and the repaired tissues were harv…

2015

Previewing distracters enhances the efficiency of visual search. Watson and Humphreys (1997) proposed that the preview benefit rests on visual marking, a mechanism which actively encodes distracter locations at preview and inhibits them afterwards at search. As Watson and Humphreys did, we used a letter-color search task to study constraints of visual marking in conjunction search and near-efficient single-feature search with single-colored and homogeneous distracter letters. Search performance was measured for fixed target and distracter features (block design) and for randomly changed features across trials (random design). In single-feature search there was a full preview benefit for bot…

Do young readers have fast access to abstract lexical representations? Evidence from masked priming

2014

Although there is consensus that adult readers have fast access to abstract letter/word representations, the developmental trajectory of such access has not been mapped out yet. To examine whether developmental readers have rapid access to abstract representations during the early stages of word processing, we conducted a masked priming lexical decision experiment with two groups of young readers (third and fifth graders) and a group of young adults. We selected two types of words: (a) words composed of cross-case letters that are visually dissimilar (DIS words; e.g., arte/ARTE [Spanish for art]) and (b) words composed of cross-case letters that are visually similar (SIM words; e.g., vivo/V…

Does Kaniso activate CASINO?: input coding schemes and phonology in visual-word recognition.

2010

Most recent input coding schemes in visual-word recognition assume that letter position coding is orthographic rather than phonological in nature (e.g., SOLAR, open-bigram, SERIOL, and overlap). This assumption has been drawn – in part – by the fact that the transposed-letter effect (e.g., caniso activates CASINO) seems to be (mostly) insensitive to phonological manipulations (e.g., Perea & Carreiras, 2006 , 2008 ; Perea & Pérez, 2009 ). However, one could argue that the lack of a phonological effect in prior research was due to the fact that the manipulation always occurred in internal letter positions – note that phonological effects tend to be stronger for the initial syllable (…