10,11 Three different commensal bacterial strains from humans (Lactobacillus salivarius, Escherichia coli and Bacteroides fragilis) were selected, selleck kinase inhibitor and their capacity to translocate in the in vitro M-cell model system and in vivo was confirmed. Results confirmed that differential translocation is evident at the level of the M cell in a pattern that is distinct from differential rates of internalization by monocytes for the same bacteria. Importantly, each bacterium was found to induce a different pattern of gene expression in M cells demonstrating for the

first time an immunosensory discriminatory function of M cells to commensal bacteria. Female BALB/c mice (Harlan, Bicester, Oxon, UK) aged 6–8 weeks were housed under specific pathogen-free

conditions and received food and water ad libitum. Mice were killed by cervical dislocation. All animals were housed in conventional animal facilities cared for in compliance with protocols and procedures approved by the Animal Experimentation Ethics Committee of University College Cork. Lactobacillus salivarius subsp. salivarius strain UCC118 was cultured PI3K inhibitor at 37° under anaerobic conditions for 24 hr in de Man–Rogosa–Sharpe broth (Oxoid, Basingstoke, UK). Escherichia coli HB101 (German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany) was cultured in lysogeny broth at 37° under aerobic conditions for 24 hr with constant shaking. Bacteroides fragilis CIT01, kindly provided by Dr Jim O’Mahony, Cork Institute of Technology was cultured at 37° under anaerobic conditions for 24 hr in brain heart infusion broth (Oxoid) supplemented with 0·05%l-cysteine SB-3CT hydrochloride (Sigma, Dorset, UK). Bacterial viability was assessed using the Live/Dead BacLight viability and counting system (Invitrogen, Paisley, UK) in 0·85% sterile NaCl solution on an Accuri Flow cytometer (BD Biosciences, Erembodegem, Belgium). Plate counts were also performed for each strain with the

respective agar plates and gave corresponding results to the Live/Dead stain protocol. The Caco-2 derivative C2BBe1 epithelial cell line (ATCC CRL-2102; American Type Culture Collection, Manassas, VA) was maintained in Dulbecco’s modified Eagle’s medium (DMEM; Gibco, Life Technologies, Carlsbad, CA) supplemented with 10% fetal bovine serum (FBS; Sigma), 100 μg/ml penicillin and 100 U/ml streptomycin (Gibco), 100 μm non-essential amino acids (Gibco) and 0·01 mg/ml transferrin (Calbiochem, San Diego, CA). C2BBe1 cells were seeded on a Millicell hanging cell culture insert (Millipore, Billerica, MA) with a 3·0-μm pore size at a density of 2 × 105 cells/insert and cultured for 21 days until the transepithelial electrical resistance was > 300 Ω·cm2 when cells were fully differentiated.

105 Group A haplotypes have a fixed gene content comprising KIR3DL3-2DL3-2DP1-2DL1-3DP1-2DL4-3DL1-2DS4-3DL2 (Fig. 4, haplotype 1), but are diversified through allelic polymorphism of the individual genes. In contrast, group B haplotypes have a variable gene content comprising several genes and alleles,

some of which are not on the A haplotype (Fig. 4, haplotypes 2–6). Hence, B haplotypes generally encode more activating KIR than the A haplotype that encodes a single activating receptor, KIR2DS4. Homozygotes for group A haplotypes (Fig. 4, haplotype 1) have only seven functional KIR genes, whereas heterozygotes for group A and group B haplotypes (Fig. 4, haplotypes 1 + 2) may have all 14 functional KIR genes. The function of SCH727965 cost the inhibitory KIR depends on the availability of their specific cognate HLA class I ligands. Given that both KIR genes at chromosome 19q13.4 and HLA genes at chromosome 6p21.3 are polymorphic and display significant variations, the independent segregation of these Obeticholic Acid cost unlinked gene families produce a great diversity in the number and type of KIR–HLA pairs in individuals. In addition to haplotypic diversity, each KIR gene exhibits considerable sequence polymorphism. As of May 2010 a total of 347 KIR sequences have been deposited into the GenBank (http://www.ncbi.nlm.nih.gov/Genbank/) and IPD-KIR

databases (http://www.ebi.ac.uk/ipd/kir/index.html). The inhibitory KIR genes are relatively more polymorphic, whereas the activating KIR genes are generally conserved. Because of the similarity in sequence of the genes there have been many reports of unequal recombinations. This has led to duplication of the genes on the same haplotype106 or to the converse of haplotypes missing Methane monooxygenase genes,

including framework genes.107 Studies in a limited number of KIR loci and populations to date support the notion that variation within and between populations in the activating KIR is maintained primarily through gene-content variation, rather than allelic diversity. In contrast, although most individuals bear the majority of the inhibitory KIRs, significant allelic polymorphism is often present at these loci. The extensive polymorphism of KIR genes and their alleles has been reviewed previously.6 The synergistic combination of allelic polymorphism and variable gene content individualizes KIR genotypes to an extent where unrelated individuals almost always have different KIR types. Furthermore, the KIR receptors are clonally expressed on NK cells, so that each NK cell clone expresses only a portion of the genes carried by the gene profile of the individual.108 Stochastic expression of different combinations of receptors by NK cells results in this repertoire of NK clones with a variety of ligand specificities. This level of diversity probably reflects a strong pressure from pathogens on the human NK cell response.

Analysis of PBMCs from healthy donors and SLE patients was done on fresh samples. Samples

from IL-2-treated patients were frozen PBMCs that had been collected immediately before treatment and 18 h, 1 week, and 2 weeks after the first infusion. All IL-2 patients received 600,000 IU/kg of rhIL-2 (Proleukin) every 8 h by intravenous bolus for up to 14 doses. Two cycles of IL-2 immunotherapy were given at 2-week intervals following which clinical response was determined and further IL-2 was administered at the discretion of their physician for patients with stable or responding disease. Enriched CD4+ or sorted cells from fresh PBMCs were cultured in 10% complete RPMI and incubated at a concentration of 100,000 cells/100 μL in 96 well plates. For pSTAT5 analysis, cells were incubated for 1 h at 37°C with or without 2 μg/mL of anti-CD25-blocking antibody (R&D Systems, clone no. 22722) and stimulated with rhIL-2 (Proleukin) for 15 min. The Ulixertinib mw cells were then fixed and permeabilized with the Fix & Perm Cell Permeabilization Reagents from Invitrogen following the methanol-modified protocol and stained for pSTAT5. For survival and proliferation assay, sorted Navitoclax cells were cultured for 7 days with or without rhIL-2 and evaluated for survival by Annexin V/7AAD staining (BD

Biosciences) and proliferation by intracellular Ki67. Frozen PBMCs from healthy individuals were thawed and cultured at 37°C in 10% complete RPMI at a concentration of 1 × 106 cells/100 μL in 96 well plates. Cells were cultured with 5 μg/mL of anti-CD28/49d alone or with Flu Vaccine (afluria®, 3 μg/mL), SEB (Toxin Techonology Inc., 1μg/mL), or CMV lysate (Advanced Biotechnologies Inc., 10 μg/mL) for 1 h, after which brefeldin A (5 μg/mL) was added. After 18 h, cells were stained for extracellular CD3, CD4, CD95, and CD25 and then stained for the intracellular cytokines IFN-γ and IL-2 after

permeabilization. CD25 MFI background was determined by staining for all markers except CD25 in each assay. Fresh PBMCs were sorted, suspended in 10% RPMI at a concentration of 50,000 cells/100 μL in 96 well plates that were uncoated or precoated with 5 μg/mL anti-CD3 (OKT3). All samples were done in triplicate with and without 2 μg/mL of anti-CD25-blocking antibody PR171 (R&D Systems, clone no. 22722). Cells were cultured for 3 days, after which 100 μL of supernatant was collected and the cells were transferred to uncoated 96 well plates and given 100 μL of fresh media with and without anti-CD25 (2 μg/mL). Two days after replating, proliferation was analyzed by counting cells with a hemocytometer and survival was determined by Annexin V/7AAD staining (Invitrogen) analyzed by flow cytometry. Statistical significance was determined by paired or unpaired student’s t-test (for comparison between two groups) or one-way ANOVA (for comparison among more than two groups) using Prism software (GraphPad, San Diego, CA, USA); a p-value of <0.05 was considered significant. Todd Triplett is a Ph.D.

Furthermore, it is an important risk factor for poor clinical outcome with ATCMR. This finding MK-2206 order suggests that it could be a useful marker for predicting the prognosis of an allograft after ATCMR. We

evaluated the severity of allograft dysfunction and tissue injury between the FOXP3 high and the IL-17 high groups, and our results showed that more severe allograft dysfunction and tissue injury were observed in the IL-17 high group compared with the FOXP3 high group. In the IL-17 high group, the tissue injury score for acute and chronic inflammation of the interstitial area and tubule was higher than in the FOXP3 high group. This finding suggests that the IL-17-dominant state is associated with both acute and chronic injuries, and previous reports may support this presumption in that acute inflammation induces the IL-17-dominant condition and, in turn hastens chronic changes in the allograft tissue in

turn.28 We also evaluated the clinical indicators of ATCMR, which represent poor prognosis (steroid-resistant ATCMR, incomplete recovery, and recurrence of ATCMR) between the FOXP3 high and the IL-17 high groups. The results showed that all indicators in the IL-17 selleck products high group were higher than in the FOXP3 high group. The reason for this result is still unclear but we speculate several possibilities. First, renal epithelial cells exposed to IL-17 can produce inflammatory mediators with the potential to stimulate early alloimmune responses.29 Second, IL-17 could rapidly recruit neutrophils, which are observed frequently in biopsies with more severe rejection.30 Third, IL-17 could drive alloimmune responses

by promoting lymphoid neogenesis.28 Therefore, it is possible that exposure to relatively higher levels of IL-17 during Cyclin-dependent kinase 3 ATCMR induces stronger alloimmune responses and results in a poor clinical outcome in ATCMR. As observed, with poor clinical outcome in the IL-17 high group, the FOXP3/IL-17 ratio also affected significantly the long-term allograft survival after ATCMR. The allograft survival rate at 1 year (90% versus 54%) and 5 years (85% versus 38%) in the FOXP3 high group was higher than in the IL-17 high group (P = 0·00) (Fig. 2d). Furthermore, multivariate analysis revealed that the FOXP3/IL-17 ratio is a significant prognostic factor independent of other important confounding factors, such as chronic tissue injury and allograft dysfunction. This suggests that the IL-17-dominant state is not secondary to the outcome of allograft dysfunction or chronic tissue injury. In patients who suffered from multiple episodes of ATCMR, the FOXP3/IL-17 ratio decreased in the repeat ATCMR compared with the first ATCMR in all patients (Fig. 3).

4 The bladder, prostate, urethra and central nervous system can be etiological organs for LUTS caused by BPH, although it is not clear if hyperplasia of the prostate is a source of

LUTS.5 Prevalence of LUTS complex is 15–60% in men aged over 40 years and prevalence rises markedly with age.5–7 The prevalence of ED is also very high and rises with age; 17–40% of 40-year-old men experience some degree PD-332991 of ED, and the rate is as high as 70–84% in 70-year-old men.8,9 In many community-based studies, the prevalence of ED is associated with the presence and severity of LUTS and the severity of BPH-induced LUTS is proportional to the severity of ED. Both BPH and ED have a significant negative impact on health-related quality of life for ageing men.10 It has not yet been confirmed how much the two disorders influence each other and what is considered the main factor in the initiation of both disorders. There has been increasing interest in the nitric oxide (NO)-cGMP pathway as a promising pharmacological target for treating BPH/LUTS. The presence

of nitric oxide synthase (NOS) has been described in detail in the human prostate by biochemical, immunohistochemical and molecular biological methods.11 In the human prostate, endothelial NOS (eNOS) is related to the maintenance of local vascular perfusion, whereas neuronal NOS (nNOS) is mainly involved in the initiation of the relaxation of smooth muscle and in the control of glandular function, including the proliferation of epithelial and subepithelial Selleck Enzalutamide cells.12 Inducible NOS (iNOS) has not been detected in normal prostate tissue, although there is evidence that iNOS is expressed in hyperplastic and malignant prostatic tissues.13 Expression of phosphodiesterase (PDE) isoenzymes in the human prostate were verified by molecular biology and protein chemistry.14 Research Phospholipase D1 has shown that mRNA transcripts encoding for PDE types 1, 2, 4, 5, 7, 8, 9 and 10 in different anatomic

regions of the human prostate, and demonstrated hydrolytic activities of PDE types 4 and 5 in cytosolic fractions of prostatic tissue.15 Smooth muscle in the corpus cavernosum, prostate and bladder are relaxed by NO.14–16 Phosphodiesterase type 5 inhibitors (PDE5 I), such as mirodenafil, sildenafil, tadalafil, and udenafil increase the concentration of cGMP in smooth muscle by blocking PDE type 5 (PDE5) enzyme, inducing erection of the penis and relaxation of the bladder neck and prostate leading to voiding. Considering the high incidence of ED and BPH in aging men, the capacity to treat both disorders simultaneously with a single agent, such as a PDE5 I, would be very valuable.17 Recently, several PDE5 I have produced statistically significant improvements in various measures of sexual function and urinary symptoms.18,19 Therefore, we evaluated the relationship between BPH/LUTS and ED, and the role of PDE5 I on BPH/LUTS. Recent large-scale epidemiological studies disclosed a powerful association between BPH/LUTS and ED.

Expression was normalized to the expression of β-actin. Specific primers for each indicated promoter

were listed in Supporting Information Table 1. Cultured T cells were harvested and stained using predetermined optimal concentrations of the respective antibodies. After Fc blocking (antimouse CD16/CD32 mAb), prepared cells were stained with the indicated mAbs: Qdot605 anti-CD4, find more allophycocyanin anti-LAG-3, and SA-allophycocyanin Cy7. For intracellular anti-Egr-2 staining, cells were stained using the Foxp3 staining buffer set (e-Bioscience). For co-staining of Egr-2 and IL-10, cells were re-stimulated for 4 h at 37°C with phorbol 12-myristate 13-acetate (PMA; 50 ng/mL; Sigma), ionomycin (500 ng/mL; Sigma), and for final 2 h with GolgiStop (1 μL/mL; BD Biosciences), followed by surface staining. Cells were then fixed with 2% paraformaldehyde for 10 min at room temperature and permeabilized with 0.5% saponin (Sigma) containing anti-Egr-2 and anti-IL-10 antibodies for 30 min at room temperature in the dark. Analysis and cell sorting of CD4+ T cells were performed using FACSVantage with CellQuest (Becton Dickinson). Data were

processed HM781-36B concentration with FlowJo software. A full gating strategy was shown in Supporting Information Fig. 1. Cytokines in culture supernatants of CD4+ T cells were analyzed using ELISA kits according to the manufacturer’s instructions (Thermo Scientific and Biolegend). The Dual-Luciferase Reporter Assay System was used (Promega). 293T cells were cultured in 96-well plates and transfected with pGL-3-(-1500 Blimp-1) crotamiton LUC reporter plasmids and phRL-(thymidine kinase) LUC control plasmids with either a pMIG vector or pMIG vector containing

Egr-2 using Fugene6 (Roche). Cells were harvested 48 h later and LUC activity was assessed using MicroLumat Plus LB96V Luminometer (Berthold). Splenocytes from C57BL/6 mice were cultured for 24 h with anti-CD3 Ab (10 μg/mL) and CD4+ T cells were then purified using the MACS system. The ChIP assay was carried out using a Simple ChIP Enzymatic Chromatin IP Kit (Cell Signaling Technology). Briefly, CD4+ T cells were fixed with formaldehyde and quenched with glycine. Crude nuclei were isolated and digested enzymatically using Micrococcal Nuclease and then sonicated to reduce chromatin DNA length to approximately 500 bp. Chromatin solutions was diluted in IP dilution buffer containing protease inhibitor and incubated with anti-Egr-2 Ab (Covance) or normal rabbit IgG. Cross-links were reversed by incubation overnight at 65°C, and immunoprecipitated chromatin (DNA) was purified by phenol-chloroform extraction and ethanol precipitation.

Preferential picking of SNPs was conducted under the pairwise tagging option, with a minimum allele frequency of 25% and a high Illumina design score. The algorithm was set to select tags that would cover the Caucasian HapMap panel with an r2 of 0·8 or greater [11]. Furthermore, for both genes one additional custom SNP was selected on the basis of previously published association studies or presumed functionality. The following

RXDX-106 in vitro SNPs were genotyped in the IL1B gene; rs1143627 (tag), rs1143634 (tag), rs1143643 (tag) and rs1799916 (custom); IL1RN: rs11677397 (custom), rs2637988 (tag), rs408392 (tag), rs397211 (tag). DNA was extracted from whole blood samples and SNP typing was conducted using a custom Illumina goldengate bead SNP assay in accordance with the manufacturer’s recommendations (Illumina Inc., San Diego, CA, USA). Serum and BALF levels of IL-1β and IL-1Ra were determined using a multiplex suspension bead array system according to the manufacturer’s protocol (Bio-Rad Laboratories, Hercules, CA, USA). Data analysis was performed find more using the Bioplex 100 system and Bioplex Manager software version 4·1 (Bio-Rad Laboratories). The lower limit of detection was 0·3 pg/ml for IL-1β and 2·2 pg/ml for IL-1Ra. Because the variation in BALF retrieval in healthy controls was not significantly

different from retrieval in IPF patients, we did not correct for that. Genotype frequencies were tested for Hardy–Weinberg equilibrium (http://ihg2.helmholtz-muenchen.de/ihg/snps.html). Genotype and allele frequencies in the IPF group were compared with the control population using the χ2 test. Haplotypes and linkage disequilibrium (LD) were calculated (Haploview 4·1; Broad Institute of MIT and Harvard, Cambridge, MA, USA). Serum and BALF data were expressed as median and IQR. Differences in serum or BALF

concentrations between patients and controls were analysed using a Mann–Whitney U-test. For analysis of correlation, log-transformation was used to Amobarbital reach near-normal distribution. The correlation between cytokines in BALF and clinical data was assessed using Pearson’s correlation coefficients. The differences between cytokine levels in different genotypes were assessed with the Kruskal–Wallis test. Statistical analysis was performed using spss version 15·0 (SPSS Inc., Chicago, IL, USA) and GraphPad Prism 5·0 (GraphPad Software, Inc., San Diego, CA, USA). Statistical significance was considered at a value of P < 0·05. Serum levels of IL-1β in IPF patients were increased significantly compared to healthy controls, while serum levels of IL-1Ra were decreased (Table 1). Furthermore, BALF levels of both IL-1β and IL-1Ra were increased significantly in IPF patients compared to healthy controls.

Were this so, females could have been relatively more attracted

to the novel rotation of the familiar shape than were males and thus have been more likely to divide attention between the novel rotation and its mirror Navitoclax in vivo image. To investigate this possibility, 3- to 4-month-olds were given an angular discrimination task in which infants were familiarized with the number 1 (or its mirror image) at one rotation and then tested with the same shape in the familiarized rotation versus the shape in a novel rotation. Infants were provided with just a single 15-s familiarization presentation of a given angular rotation because that was the length of time infants were exposed to a given angular rotation in the familiarization portion of the mental rotation experiment in Quinn and Liben. Figure 3 depicts an example of the task used in Experiment 1. Participants were 24 3- to 4-month-olds, including 12 females, mean age = 114.75 days, SD = 10.13 days, and 12 males, mean age = 117.75 days,

SD = 8.39 days. The sex difference in age was not significant, t(20) = −0.94, p > .20, two-tailed. Data from three additional infants who were tested (one female) were excluded from analyses because they consistently (≥95%) favored one side of the display (N = 2) or failed to compare the test stimuli at all (N = 1). Most infants in PD-0332991 manufacturer both Experiments 1 and 2 were Caucasian and from middle-class backgrounds. Each stimulus consisted of a black number 1 (or its mirror image) in a particular degree of rotation that was centered on a 17.7 × 17.7 cm white posterboard. The number 1 was 5.2 cm high and 3.2 cm wide at the base. The width of both the base and stem of the number 1 was 1.2 cm. Infants were tested in a visual preference apparatus, modeled after that of Fagan (1970). The apparatus has a gray display panel which includes two compartments to hold the stimuli. The stimuli

were illuminated by a fluorescent lamp Cyclin-dependent kinase 3 that was shielded from the infant’s view. Center-to-center distance between compartments was 30.5 cm, and on all trials, the display panel was situated approximately 30.5 cm in front of the infant. There was a 0.62 cm peephole located midway between the compartments that permitted an observer to record infant visual fixations. A second peephole, 0.90 cm in diameter, located directly below the first peephole, permitted a Pro Video CVC-120PH pinhole camera and Magnavox DVD recorder to record infant gaze duration. Familiarization consisted of a single 15-s familiarization trial, during which two identical copies of the number 1 (or its mirror image) were presented in a specific degree of rotation. There were two 10-s preference test trials, each of which paired the familiarized rotation with a novel rotation.

There is no proven vaccination technique that can prevent and/or cure endogenous ag–caused disorders [28, 31, 61–65]. However, www.selleckchem.com/products/z-vad-fmk.html some recently instituted vaccination techniques provide a glimmer of hope in providing future possibilities for the prevention and treatment of chronic ailments [66–71]. E.g. one of the vaccination techniques – being able to induce oral tolerance – proved itself to be effective in animal experiments, especially in preventing and delaying the occurrence of autoimmune diseases; but its effectiveness in treating humans with autoimmune conditions so far has not resulted

in significant clinical improvements [67]. For this reason, endogenous ag–initiated disorders are treated with cytotoxic and immunosuppressive agents. These treatment modalities provide no specific cures and often have undesirable side effects.

Would we be able to terminate the pathogenic IgG aab response in an autoimmune disease e.g. in SPHN, then the continuance of the disease process would come to a halt and a recovery from the disease would ensue. According to some scientists, once an autoimmune disease is initiated and maintained, e.g. by emerging autoreactive T cells or by pathogenic IgG aabs [72, 73] (produced by long lived plasma cells), the autoimmune disease causing process cannot be halted, only interfered with somewhat by anti-inflammatory medications. However, there are those who believe that ag-specific downregulation selleck products of autoimmune diseases is possible, e.g. if the inciting agent is removed (it could be a drug) [24], or if the target ag is presented in a suitable

Clomifene format (which only works if the ag is presented in a soluble form prior to induction of an experimental autoimmune disease) [36–41]. We share this belief that ag-specific downregulation or upregulation of immune responses in certain autoimmune disorders (i.e. autoimmune disease and cancer) are possible and our experiments have shown these to be true through the utilization of the modified vaccination technique (MVT) [21, 44, 51]. We have shown that by a predetermined ab inducing/maintaining technique:  specific IgM aabs can be produced to eliminate disease contributing aag [44, 51, 52]; and similarly To achieve desired corrective immune responses, the etiologies and pathogenesis of the autoimmune disorders must be understood as well as how to produce the essential components that are able to evoke the appropriate preventative and/or therapeutic outcomes. The immune system unconditionally responds to the right antigenic ‘information’. The challenge was to find how the normally functioning immune system could be affected – by the presentation of the antigenic ‘information’– to respond and correct endogenous ag–caused mishaps.

In this present study, we characterise the global transcriptional signatures at this time point in ovine afferent lymph cells as they migrate from the injection site into the lymphatics following vaccination with a liposome antigen formulation incorporating CpG. We show that at 72h post vaccination,

liposomes alone NVP-LDE225 supplier induce no changes in gene expression and inflammatory profiles within afferent lymph; however the incorporation of CpG drives interferon, antiviral and cytotoxic gene programs. This study also measures the expression of key genes within individual cell types in afferent lymph. Antiviral gene signatures are most prominent in lymphocytes, which may play a significant and unexpected role in sustaining the immune response to vaccination at the site of injection. These findings provide a comprehensive analysis of the in vivo immunological pathways that connect the injection site with the local draining lymph node following vaccination.

This article is protected by copyright. All rights reserved. “
“IFN-α/β link innate and adaptive immune responses by directly acting on naïve CD8+ T cells. This concept unveiled in mice remains unexplored in humans. To investigate that, human CD8+CD45RO− cells were stimulated with beads coated with anti-CD3 and anti-CD28 mAb, mimicking Ag (type-1) and FK866 in vivo co-stimulatory (type-2) signals, in the presence or absence of IFN-α and their transcriptional profiles were defined by cDNA-microarrays. We show that IFN-α provides a strong third signal directly to human CD8+ T cells resulting in regulation of critical genes for their overall activation. This transcriptional effect was substantiated

at the protein level and verified by functional assays. Interestingly, the biological effects derived from selleck screening library this stimulation vary depending on the CD8+ T-cell population. Thus, whereas IFN-α increases the proliferative capacity of naïve CD8+ T cells, it inhibits or does not affect the proliferation of Ag-experienced cells, such as memory and effector CTL, including CMV-specific lymphocytes. Cytolysis and IFN-γ-secretion of all these populations are enhanced by IFN-α-derived signals, which are critical in naïve CD8+ T cells for acquisition of effector functions. Our findings in human CD8+ T cells are informative to understand and improve IFN-α-based therapies for viral and malignant diseases. Type I IFN (IFN-I) comprises a cytokine family that in humans includes 13 IFN-α subtypes and single proteins for IFN-β, IFN-ε, IFN-κ and IFN-ω 1. IFN-α/β are produced in response to viruses and are critical for viral defense. IFN-I signals through a common receptor (IFNAR) composed of two subunits, IFNAR1 and IFNAR2 2. The JAK-STAT pathway is critical for IFNAR signaling 3.