(Grade A*). The blood pressure (BP) of people with type 2 diabetes should be maintained within the target range. ARB or ACEi should be considered as antihypertensive agents of first choice. Multi-drug therapy Rapamycin should be implemented as required to achieve target

blood pressure. (Grade A*) People with type 2 diabetes should be informed that smoking increases the risk of chronic kidney disease (CKD) (Grade B*). The HbA1c target may need to be individualized taking in to account history of hypoglycaemia and co-morbidities. (refer to NHMRC Evidence Based Guideline for Blood Glucose Control in Type 2 Diabetes at http://www.nhmrc.gov.au). This guideline topic has been taken from the NHMRC ‘National Evidence Based Guidelines for Diagnosis, Prevention and Management of CKD in Type 2 Diabetes’ which can be found in full at the CARI website (http://www.cari.org.au). The NHMRC guideline covers issues related to the assessment and prevention of CKD in individuals with established type 2 diabetes. The NHMRC guidelines do not address the care of people with diabetes who have end-stage kidney disease or those who have a functional renal transplant. In addition, the present guideline does not provide recommendations regarding the management of individuals with established CKD, with

LY2606368 cell line respect to the prevention of other (non-renal) adverse outcomes, including retinopathy, hypoglycaemia, bone disease and cardiovascular disease. It is important to note however, that in an individual with type 2 diabetes, the prevention of these complications may be a more important determinant for their clinical care. Consequently, the recommendations made must be balanced against the overall management needs of each individual patient. It should be noted that the best way to prevent CKD in individuals with diabetes is to prevent diabetes. NHMRC recommendations for the primary prevention of type 2 diabetes are available

elsewhere (http://www.diabetesaustralia.com.au). These guidelines specifically target the management of individuals with established Elongation factor 2 kinase type 2 diabetes. A risk factor analysis for kidney dysfunction in type 2 diabetes following 15 years of follow up from the UKPDS study,1 identified systolic blood pressure; urinary albumin excretion and plasma creatinine as common risk factors for albuminuria and kidney impairment (creatinine clearance and doubling of plasma creatinine). Additional independent risk factors for kidney impairment were female gender, decreased waist circumference, age, increased insulin sensitivity and sensory neuropathy. A cross-sectional study of 1003 Japanese hospital patients with type 2 diabetes2 identified large waste circumference and elevated BP as risk factors for microalbuminuria while dyslipidaemia was identified as a risk factor for decreased glomerular Filtration Rate (GFR).

Since its first meeting in 1994, the aim of this Conference has been to allow young scientists and trainees from this region to meet with world class scientists and have selleck chemicals the opportunity, not only to listen to their cutting-edge lectures but also to continue with rather informal discussions during the mid day hiking trips to the surrounding spectacular mountains, rustic villages, or castle ruins (Fig. 1). Since 1998, the Tatra Conference has been held as a regular EFIS meeting, receiving monetary

support since 2008 from the European Journal of Immunology by way of the EFIS-EJI partnership, leading it to be called the EFIS-EJI Tatra Immunology conference. It is currently held every two years, with a schedule that Smoothened Agonist includes morning and late-afternoon lectures by invited speakers, poster presentations by other participants (Ph.D. students, postdocs, and medical residents), and informal discussions; all still combined with the extended midday recreational activities, i.e. hiking trips (Fig. 2). The aim of the organizers is to have a style similar to that of the Gordon

Conferences. The number of participants is limited to approximately 120 (Fig. 3), with the majority of the students and trainees coming from the Czech Republic, Slovakia, and Austria, supported by travel grants provided by EFIS-EJI, national immunology societies, and by the participants’ institutions; however, there is increasing interest among students from other countries such as Germany, The Netherlands, and UK to participate. Sadly, despite our best

efforts, intense advertising, and generous travel grants offered by EFIS-EJI, we fail to attract large number of participants from Eastern Europe and post-Soviet countries. The 3-day scientific programmes at all EFIS-EJI Tatra Conferences have had sessions ranging from fundamental to clinical immunology; however, in the past few meetings, the major goal of the scientific program has been to document the importance of basic and clinical research for the development of novel diagnostic and therapeutic strategies in clinical medicine. This report highlights some Methane monooxygenase of the key presentations of the 9th EFIS-EJI Tatra Immunology Conference held at Štrbské Pleso in the High Tatra Mountains, Slovakia; from September 4–8, 2010, and organized by myself together with Václav Hořejší (Czech Immunological Society), Falk Nimmerjahn (Erlangen, Germany), Stanislava Blažíčková, Zuzana Popracová, Zuzana Polčíková (Slovak Immunological Society), and Hannes Stockinger (Austrian Society for Allergology and Immunology). Recent advances in basic immunology To begin the conference, Kevin Woollard (London, UK) described current models of the development and functions of mononuclear phagocytes. Current models propose that blood monocytes, many macrophage subsets, and most DCs originate in vivo from hematopoietic stem cell (HSC)-derived progenitors with myeloid-restricted differentiation potential.

The frequency of β7high cells was higher among the dividing gTG-stimulated CD4+CD45RO+ memory T cells (median 35·4%, range 6·2–85·8%) than among TT-stimulated memory T cells (median 25·6, range 2·9–49·8%) (P = 0·021; Mann–Whitney U-test) in children with CD. A similar trend was also observed in control children with a median 39·3% (range 0·0–80·0%) and 17·1% (range 0·0–89·3%) of gTG- and TT-stimulated cells expressing β7 integrin, respectively (P = 0·062) (Fig. 4). There was no difference in β7 expression on proliferating TT-stimulated T cells between

the study groups (P = 0·72). Collectively, the higher expression of β7 integrin supports the notion that circulating memory CD4+ T cells specific to gTG migrate selectively to the small intestine, where they have also presumably been primed. Multiple studies have demonstrated that CD4+ T cells specific to gTG epitopes can be detected click here in the peripheral blood of adult CD patients [10–12]. In this study, we show for the first time that these cells are also detectable in the peripheral blood of children with newly diagnosed CD. Moreover, in children with CD CD4+ T cells

specific to gTG have mainly a memory phenotype and express high levels of the gut-homing molecule β7 integrin, supporting the in-vivo significance of our study. The current dogma on the pathogenesis of CD suggests that deamidation of gliadin by TTG leads to the conversion of glutamine residues to negatively charged glutamic acid residues. This, in turn, facilitates the binding of gliadin peptides to the disease-associated SAHA HDAC cell line DQ2 and DQ8 molecules that prefer negatively charged amino acids in their binding pockets [19]. In line with this model, we observed responsiveness more often to gTG than to native gliadin but, notably, this was seen only in CD children (Table 1). More than half the patients with Protirelin CD had CD4+ T cell responses to gTG, whereas the frequency of positive responses in healthy control children was lower and comparable to the frequency of responses to native gliadin (∼20%). Our results with native gliadin are

in accordance with a study where responsiveness to this antigen was common in healthy control subjects [20]. Importantly, studies by Anderson et al. reported that after an oral gluten challenge some of the healthy controls had specific responses to native gliadin, whereas responses to gTG increased exclusively in patients with CD [11]. An elegant study by Ráki et al. confirmed these findings using HLA-tetramers to detect CD4+ T cells specific to gTG epitopes in the peripheral blood of CD patients, but not in controls, after a short-term gluten challenge [12]. Although CD4+ T cell responses to gTG have been demonstrated readily in the peripheral blood after gluten challenge, no responses were detected in CD patients on a gluten-free diet [10–12].

The most central angiogenic factor

in skeletal muscle capillary growth is VEGF. During muscle contraction, VEGF increases in the muscle interstitium, acts on VEGF receptors on the capillary endothelium, and thereby stimulates angiogenic processes. A primary source of muscle interstitial VEGF during exercise is the skeletal muscle fibers which contain large stores of VEGF within vesicles. We propose that, during muscle activity, these VEGF-containing vesicles are redistributed GDC-0941 supplier toward the sarcolemma where the contents are secreted into the extracellular fluid. VEGF mRNA expression is increased primarily after exercise, which allows for a more rapid replenishment of VEGF stores lost through secretion during exercise. Rapamycin concentration Future studies should

focus on elucidating mechanisms and regulation of VEGF secretion. “
“The purpose of this study was to visualize glomerular hyperfiltration in rats at the early stage of diabetes under in vivo conditions and to quantitatively examine the effect of C-peptide on filtration. Type 1 diabetes was induced by streptozotocin (50 mg/kg) in Wistar rats. The rats were divided into four groups: control, control plus C-peptide, early diabetes, and early diabetes plus C-peptide. C-peptide was continuously infused (50 pmol/kg/min). Filtration was visualized by a bolus shot of various sizes of dextrans (3 k to 70 k Da) conjugated with Texas Red and observed with a multiphoton microscope under inhaled anesthesia. Relative sieving coefficients were used to quantify filtration. Almost all smaller particles (3–10 k Da) were filtered both in control and diabetic rats. Filtration of larger particles (40–70 k Da) was seen in normal rats but was more apparent in diabetic rats, where it was progressive according to the duration of diabetes. C-peptide administration

restored Docetaxel ic50 the leakage of larger particles to the level seen for the control. We visualized and analyzed hyperfiltration and confirmed that C-peptide has a nephroprotective effect. Furthermore, we found that the leakage of larger particles increased as the duration of diabetes increased. “
“Please cite this paper as: Copp, Hirai, Ferguson, Musch and Poole (2011). Role of Neuronal Nitric Oxide Synthase in Modulating Microvascular and Contractile Function in Rat Skeletal Muscle. Microcirculation 18(6), 501–511. Objective:  This investigation tested the hypothesis that selective nNOS inhibition would lower the dynamic microvascular O2 delivery/utilization () balance (which sets the Po2mv) in rat skeletal muscle at rest and during contractions.

The purity of cells was verified by flow cytometry selleck kinase inhibitor and ranged from 97 to 99.5% for monocytes, with less than 1% CD3-positive cell contaminants in NK cells (data not shown). Monocytes were then induced to differentiate into MΦs and DCs by culture for 6 days in RPMI 1640 Glutamax I, 1% penicillin-streptomycin,

10 mM HEPES, 1% nonessential amino acids and 10% FCS (all from Invitrogen), supplemented with 50 ng/mL M-CSF and 10% autologous decomplemented plasma for MΦs, or with 1000 IU/mL GM-CSF and 500 IU/mL IL-4 (all from PeproTech, London, UK) for DCs. We replaced 40% of the medium, and the cytokines, every 48 h. NK cells were frozen in 90% FCS, 10% DMSO (Sigma, Saint-Quentin Fallavier, France) and stored in liquid Selleck PKC412 nitrogen until coculture with DCs or MΦs.

DCs and MΦs were harvested and incubated for 1 h at 37°C with virus-free VeroE6 cell supernatant (mock), LASV or MOPV at a MOI of 2, unless otherwise specified. NK cells were then thawed and cocultured with mock-, LASV-, or MOPV-infected APCs (106 cells/mL), at an NK-cell:APC ratio of 1:5. In some conditions, DCs and MΦs were stimulated with 1 μg/mL LPS (Sigma), NK cells were activated by incubation with 200 IU/mL IL-2 (PeproTech) and 1 μg/mL PHA (Sigma) or were stimulated with 10 μg/mL polyI:C, 15 μg/mL imiquimod or 1 μg/mL ssRNA40 (InvivoGen, Toulouse, France). We used 20 pg/mL PMA (Sigma) and 720 ng/mL ionomycin (Sigma) or 50 ng/mL IL-12 (PeproTech) and 50 ng/mL IL-18 (MBL, Naka-ku Nagoya, Japan) to stimulate NK cells. In some experiments, contact between NK cells and APCs was prevented by

a polycarbonate membrane with 0.4-μm pores (Corning Life Sciences, Schiphol-Rijk, The Netherlands). In some conditions, CXCR3 was blocked with 5 μg/mL anti-CXCR3 mAb (R&D Systems, Lille, France). Cell contacts were blocked with 5 μg/mL anti-CD40L, 10 μg/mL anti-NKG2D (R&D Systems), 2 μg/mL anti-NKp30, anti-NKp44, or anti-NKp46 Ab (Miltenyi Biotech). The effect of type I IFN was prevented with 2.5 μg/mL anti-IFN-α mAb (PBL Biomedical Laboratories, Piscataway, NJ) and 5 μg/mL anti-CD118 aminophylline Ab (IFNα/β-R chain 2) (PBL) and a combination of anti-CXCL9, anti-CXCL10, and anti-CXCL9 mAbs (8 μg/mL each, R&D Systems) was used to neutralize CXC chemokines. We used irrelevant IgG2a Ab (R&D Systems) for control experiments. Seventy-two hours after seeding, cells were harvested, washed, and the final pellets were resuspended in 5% human serum in PBS. The expression of cell surface molecules was analyzed by incubating cells for 30 min at 4°C with various Ab. NK cells were gated as CD3− and CD56+ cells, using FITC- or PE-Cy7-conjugated CD3 Ab (Beckman Coulter, Marseille, France) and Alexa Fluor 488-, Alexa Fluor 647-, or PE-Cy5-conjugated CD56 (BD Pharmingen, San Diego, USA).

The visual analog scale of UDI-6 and IIQ-7 has been shown to be reliable and reproducible compared to the Likert-type supporting its use in urogynecologic research.[34] Many studies have emerged over the past decade that have incorporated QOL questionnaires to determine their relationship to symptoms, to evaluate and compare efficacy of different treatment modalities and to investigate their potential use in predicting the presence of physical objective findings. The nearly universal acceptance of the POP-Q system of staging of prolapse combined with the consistent use

of standardized and validated QOL questionnaires has facilitated the evaluation of findings across study designs thereby increasing their potential to influence clinical practice. Several studies have investigated the relationship between Carfilzomib scores on QOL questionnaires, subjective symptoms and findings on physical examination. Symptoms that women with POP experience have been commonly thought to be related to specific compartments (i.e. UI) (and other voiding dysfunction) and bowel dysfunction were due to anterior and posterior

compartment prolapse, respectively. However, earlier studies reported few correlations between symptoms of pelvic floor dysfunction and the presence of POP.[35-37] These findings are similar to results from a more recent prospective cross-sectional Osimertinib molecular weight study evaluating the relationship between bowel complaints and the severity of prolapse. Three hundred and twenty-two mostly Caucasian women with stage I through IV prolapse by POP-Q were asked

to complete the Colorectal-Anal Distress Inventory and Colorectal-Anal Impact Questionnaire.[38] Although almost one-third of women answered “yes” to the question “Do you usually have to push on the vagina or around the rectum to have or complete a bowel filipin movement?”, a prevalence consistent with other studies,[39, 40] there was no association between a more advanced stage of prolapse and increased questionnaire scores or bowel symptoms. These results may in part be due to the fact that the “severity of prolapse” may be too broad a category and more specific physical findings should be targeted. In support of this, Saks et al. found that using the short form PFDI-20 to screen 260 women with POP, those with posterior vaginal wall prolapse were more likely to report straining on defecation, incomplete emptying and splinting with defecation.[41] Thus, in the absence of posterior compartment prolapse, symptoms of bowel dysfunction may not be an associated feature of advanced POP. Barber et al. investigated whether a single question could screen for the presence of POP without a physical examination.

In addition to the burden on health care systems, GI infection in domestic animals is responsible for losses in agriculture. Although drug treatment is relatively efficient and of low cost for control of infection by GI parasites, this strategy is not sufficient to control transmission because human populations living in endemic areas are constantly being reinfected. Hence, studies focused on the understanding BAY 73-4506 molecular weight of immunological mechanisms associated with the protection of the human

host are of great importance. Strongyloides venezuelensis, a nematode that naturally infects wild rats, is frequently used in experimental studies as its life cycle is well characterized and easily maintained in laboratory rodents. In a natural setting, eggs hatch from contaminated faeces, and larvae moult through different stages from L1 until L3. These L3 larvae can infect the host or become adults, mate and produce eggs outside of the host. Infection usually occurs by penetration of filiform larvae (L3 infective) through the skin of the host. Similar to Strongyloides stercoralis in humans, S. venezuelensis larvae have an obligatory migration through the rodent lungs before establishment in the duodenal mucosa. Adult worms then produce eggs, which will be eliminated in the faeces completing the life cycle of this parasite. In experimentally infected mice, the lung phase occurs approximately 48 h after infection and adult worms are eliminated spontaneously

from the host intestine after 12–14 days (7). The immune responses induced by nematode parasites are predominantly regulated by Th-2 cytokines, Ibrutinib solubility dmso including IL-4, IL-5 and IL-13 (8,9). Experimental studies showed that the main immunological alterations induced by GI infection are eosinophilia, intestinal mastocytosis and IgE production (10–13). However, immunological mechanisms responsible for parasite elimination are not completely elucidated and may be different for each nematode (14,15). Infection with S. venezuelensis

in mice or rats induces increased IgE levels in bronchoalveolar lavage fluid (BALF) (16) and Bcl-w in serum, as well as lung and intestinal eosinophilia (17). Moreover, a Th2-polarized response is associated with host protection, which is seen in patients infected by S. stercoralis (18–20) as well as in experimental models (16,17,21). After the elimination of S. venezuelensis adult worms from primary infection, the rodent host develops protective immunity against reinfection, which is demonstrated by the strong decrease in parasite burden during the challenge infection (16,22,23). In this reinfection model, the parasites are killed mainly during larvae migration and the few worms that reach the host’s intestine have reduced fecundity and are eliminated prematurely (22,24). Understanding the anti-parasitic response induced against the migrating larvae is required to identify new therapeutic strategies and targets capable of controlling frequent reinfection.

The first injection (100 μg STA-9090 supplier subcutaneously) was given at three months of age followed by four boosts (25–50 μg intraperitoneally) at 4-week intervals. Serum was withdrawn prior the fourth booster and kept overnight at 4 °C until antibody

analysis the following day. The mice were exanguinated three days after the fourth booster. ZnT8-peptide antibodies were detected in mouse serum by a standard in-house ELISA using the same ZnT8R, W and Q (aa 318–331) peptide antigens as for the immunization at Innovagen AB. The ZnT8 Triplemix RBA for mouse serum was carried out described in detail [16]. Protein A Sepharose 40% (Invitrogen, Carlsbad, CA, USA) was added for precipitation of the antibody–peptide complex. Six newly diagnosed T1D patients (<18 years of age at onset) positive for either ZnT8RAb or ZnT8WAb (Table 1) were analysed for reactivity against ZnT8 (aa 318–331) and ZnT8 (aa 268–369) proteins in a competitive RBA. The PLX3397 cost patients (33% males) were genotyped for HLA in a previous study [15] (Table 1). This patient study was approved by the Regional Ethics Board

of Stockholm. Informed consent was given by the parents of the T1D children. The preparation of all three pThZnT8 plasmids (pThZnT8R, pThZnT8W, pThZnT8Q) was carried out as described in [16]. 35S-methionine (radiolabelled) long ZnT8 (aa 268–369) proteins and cold (unlabelled) long ZnT8 (aa 268–369) proteins (Fig. 1) were produced using the TnT® Coupled Reticulocyte Lysate System as described by the manufacturer (Promega) for in vitro transcription and translation. Briefly, pThZnT8 plasmids were added in the same concentrations (final 0.02 μg/μL) and incubated for 90 min at 30 °C by shaking with either radiolabelled or cold methionine, Paclitaxel manufacturer followed by gel-separation on Illustra™ NAP-5 Columns (GE Healthcare Bio-Sciences AB, Uppsala, Sweden). Incorporated radioactivity in radiolabelled ZnT8 proteins was determined in a 1450 MicroBeta Counter (Perkin Elmer, Shelton, CT, USA). Radiolabelling

with 35S-methionine guided the labelling with cold methionine. Cold methionine was used in parallel in vitro transcription translation using the same batch as the radiolabelled methionine. The rate incorporation was computed from the specific radioactivity supplied by the vendor (Perkin Elmer) and expressed in pmol per litre anticipated (pmol/l). Competitive RBA were conducted to determine the cold peptides’ ability to compete with the radiolabelled proteins in binding to ZnT8Ab in human sera. By reciprocal permutation design, both ZnT8R and ZnT8W (aa 318–331) peptides at concentrations of 1.5–100 μg/ml, corresponding to approximately 0.98–62.5 μm/l, were incubated with radiolabelled ZnT8R or ZnT8W (aa 268–369) proteins and sera in a competitive RBA.

40,41,43 The indirect pathway is supported by observations that in many cases there is no evidence of a specific microbial antigen, and the iNKT cell response involves IFN-γ but not IL-4 production and appears to be completely dependent on costimulation by cytokines such as IL-12p70.41,45 However, because it is difficult to rule out the possibility that microbes for which no iNKT cell antigen has been identified nevertheless do contain cryptic antigens, while microbes

that do contain such antigens will also concurrently provide TLR-mediated stimulation that activates DC cytokine production, it is not clear that these two pathways are actually separate during most physiological infections. selleck kinase inhibitor For example, it has recently been shown that CD1d-mediated presentation of a lipo-peptido-phosphatidylinositol from Entamoeba histolytica is necessary for secretion of IFN-γ by iNKT cells, but that the response requires simultaneous TLR-induced IL-12 secretion.72 Similarly, in a mouse model of tuberculosis it has recently been shown that iNKT cells have a protective effect through recognition of infected macrophages, and that macrophage production of IL-12 and IL-18 is critical for this effect.73 It is not clear whether recognition of mycobacterial

antigens is required for the iNKT cell-mediated protection; however, a previous study has identified mycobacterial lipids that may serve as iNKT antigens.74 Thus, it seems likely that the two

LEE011 pathways of iNKT cell activation are not mutually exclusive, and that they occur simultaneously in many systems. Notably, it is not yet clear whether either the direct or indirect pathways of iNKT cell activation during microbial infection result in the maturation of pro-inflammatory DCs, such Ponatinib price as those that are observed after administration of α-GalCer. Induction of a pro-inflammatory DC phenotype was shown in one system to depend on the up-regulation of CD40L expression by iNKT cells as well as their secretion of cytokines such as IFN-γ, both of which are induced by a strong TCR stimulus.65 While self-antigen recognition in the presence of IL-12 and IL-18 is sufficient to induce iNKT cell IFN-γ secretion, the extent to which this form of stimulation also induces cell surface CD40L up-regulation remains unclear. Nevertheless, it is possible that, when combined with a TLR stimulus and IFN-γ, even weak CD40L stimulation from iNKT cells is sufficient to induce the maturation of pro-inflammatory DCs (Fig. 1b). Although mature DCs have the capability to potently activate naïve T cells, it is well established that immature DCs have tolerizing effects.75 Thus, by inducing maturation of immature DCs, iNKT cells may tend to promote pro-inflammatory responses simply by shifting the balance away from the more tolerizing stage of DC differentiation.

The concurrence of the C57BL/6 strain background, especially the peculiarities associated with their Treg cell subset, can also be considered. In conclusion, these results indicate this website that the prime-boost BCG/DNAhsp65 is able to protect NOD mice against type 1 diabetes, although

a more detailed investigation will be necessary to clarify the immunological mechanisms. Our findings suggest that apoptosis of diabetogenic T cells and activity of Treg cells could be involved. The authors would like to thank to Secretaria da Saúde do Estado de São Paulo for providing BCG. We are also thankful to Ana Paula Masson for her technical assistance. This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). None. “
“Two selleck kinase inhibitor subsets of CD8+ T cells are generated early

during an immune response; one of these subsets forms the memory pool, known as memory precursor effector cells (MPECs), identified by high expression of CD127 and low expression of KLRG1, whereas the other subset forms short-lived effector cells (SLECs) identified by low expression of CD127 and high expression of KLRG1. Here, we studied in vivo the role of type-I IFN in this fate decision. We found that under priming conditions dominated by type-I IFN, as observed in lymphocytic choriomeningitis virus (LCMV) infection, type-I IFN signaling directly Nitroxoline impacted the regulation of T-bet and thus the early fate decision of CD8+ T cells. In the absence of type-I IFN signaling, CD8+ T cells failed to form SLECs but could form MPECs that give rise to functional memory CD8+ T cells. Together, these findings identify type-I IFN as an important factor driving SLEC differentiation and thus instructing the early division between the effector and memory precursor CD8+ T-cell pool. In response to an acute infection CD8+ T cells rapidly expand

to form a pool of effector cells with cytolytic and cytokine secretion activity. The pool of early effector cells can be divided into two main subsets according to their ability to form terminally differentiated effector cells or long-lived memory cells; referred to as short-lived effector cells (SLECs), CD127low and KLRG1high, and as memory precursor effector cells (MPECs), CD127high and KLRG1low, respectively 1, 2. There is strong evidence that inflammatory cytokines present during CD8+ T-cell priming play a key role in the effector and memory fate decision process 3–5. In support of this notion it has been shown that IL-12 signaling is mandatory for driving activated CD8+ T cells toward an SLEC phenotype upon infection with Listeria monocytogenes but not vesicular stomatitis virus (VSV), vaccinia virus (VV) or lymphocytic choriomeningitis virus (LCMV) 5.