The concept that pregnancy is associated with immune suppression has created a myth of pregnancy as a state of immunological weakness and therefore of increased susceptibility to infectious diseases. To discuss this question we will first

review some fundamental concepts associated with Vadimezan datasheet the immune system and pregnancy. A fundamental feature of the immune system is to protect the host from pathogens. This function depends upon the innate immune system’s capacity to coordinate cell migration for surveillance and to recognize and respond to invading microorganisms. During normal pregnancy, the human decidua contains a high number of immune cells, such as macrophages, natural killer (NK) cells and regulatory T cells (Treg).1–3 Seventy percent buy Crenolanib of decidual leukocytes are NK cells, 20–25% are macrophages and 1.7% are dendritic cells.2,4,5 From the adaptive immune system, B cells are absent, but T lymphocytes constitute about 3–10% of the decidual immune cells.6 During the first trimester, NK cells, dendritic cells and macrophages infiltrate the decidua and accumulate around the invading trophoblast cells.7,8 Deletion of either macrophages, NK cells or dendritic cells (DC) has deleterious effects.9–14 Elegant studies have shown that in the absence of NK cells, trophoblast cells are not able

to reach the endometrial vascularity leading to termination of the pregnancy.12 These studies suggest that uNK cells are critical for trophoblast invasion in the uterus. Similarly, depletion of DCs prevented

blastocyst implantation and decidual formation.15 Indeed, this study suggests that uDC are necessary for decidual formation and may affect the angiogenic response by inhibiting blood vessel maturation.15 More recently, Collins et al. demonstrate that uDC association with T cell responses to the fetal ‘allograft’ starkly contrast with their prominent role in organ transplant rejection.16 These data further support the idea that the fetal–maternal immune interaction is more complex than the comparison to transplant allograft. Consequently, the presence of immune cells at the implantation old site is not associated with a response to the ‘foreign’ fetus but to facilitate and protect the pregnancy. Therefore, the immune system at the implantation site is not suppressed, on the contrary it is active, functional and is carefully controlled. Is the systemic immunity of the mother suppressed? Although we can find numerous studies describing the factors inducing immune suppression (including progesterone, defined as the natural immune suppressor), medical and evolutionary aspects are against the concept of immune suppression.

6 ± 1.7). Interestingly, in cells infected with E22ΔfliC for 2 h, IκB-α levels (13.7 ± 1.8) were lower than during E22 WT infection. However, at 4 h of infection with E22ΔfliC, IκB-α levels were higher (16.7 ± 0.2) than in cells infected see more with E22 WT (Fig. 5A, B). This indicates that both EPEC strains (E2348/69 and E22) provoke a strong and prolonged activation of NF-κB. E22 flagellum appeared to be required

to sustain the degradation of IκB-α at later stages of infection. To corroborate NF-κB activation, we also performed WB analysis of total and phosphorylated IκB-α (Fig. 5C). In mock-infected cells, we detected a clear and marked band of IκB-α (normalized band intensity value of 0.306 ± 0.016), but only a faint band of phosphorylated IκB-α (0.135 ± 0.40). In cells treated with HB101, no significant changes in phosphorylation of IκB-α (0.136 ± 0.033 at 2 h, and 0.129 ± 0.021 at 4 h) or IκB-α total levels (0.312 ± 0.054 at 2 h, and 0.315 ± 0.076 at 4 h) were detected. However, EPEC E2348/69 infection produced an intense IκB-α phosphorylation at 4 h (1.577 ± 0.117). This effect was accompanied by almost complete IκB-α

degradation (0.080 ± 0.070), indicating that all the remaining IκB-α was phosphorylated and markedly detected by the polyclonal anti-phospho-IκB-α antibody. However, at 2 h post-infection, only the degradation of IκB-α (0.232 ± 0.036) was observed, but no phosphorylation. During E22 WT infection, the degradation of IκB-α was not significantly different at 2 h of infection (0.389 ± 0.137); however, at 4 h, IκB-α Z VAD FMK degradation was lower (0.235 ± 0.038). p-IκB-α was clearly present already at 2 h (1.370 ± 0.076) Ureohydrolase and remained at 4 h (0.618 ± 0.043). These results confirm that E2348/69 as well as E22 infection promotes IκB-α phosphorylation and degradation. Since IκB-α phosphorylation and degradation are coupled, we only analysed IκB-α degradation in cells infected with E22 Δeae, ΔescN, ΔespA and ΔfliC mutants for 4 h (Fig. 5D). Contrary to the effect caused by E22 WT (0.235 ± 0.038), infection

with the intimin mutant did not induce IκB-α degradation (0.589 ± 0.238), and this value was higher than in mock-infected cells (0.306 ± 0.016). However, E22ΔescN, E22ΔespA and E22ΔfliC mutants induced lower IκB-α degradation than E22 WT strain (E22ΔescN: 0.289 ± 0.008, E22ΔespA: 0.278 ± 0.010 and E22ΔfliC: 0.275 ± 0.011). These data indicate that whereas T3SS and flagellin were confirmed to be implicated in the full activation of NF-κB, intimin decreases the activation of NF-κB. To understand the relationship between NF-κB and the activation of ERK1/2 with synthesis and secretion of proinflammatory cytokines during EPEC infection (for 4 h), we determined il-1β, il-8 and tnf-α expression by RT-PCR. Mock-infected cells expressed il-1β (Fig. 6A) and il-8 (Fig. 6C) mRNA (normalized intensity of the products: 0.680 ± 0.181 for il-1β and 0.593 ± 0.111 for il-8), but tnf-α mRNA was not detected in mock-infected cells (Fig. 6E).

This leads us to speculate that with tools of the appropriate sensitivity,

one should be able to find a large number of autoreactive T cells, even in a normal repertoire, maintained in a tolerant state by nondeletional mechanisms. Mice from the NIAID contract facility (Taconic Farms, Germantown, NY, USA) were housed pathogen free. B10.A CD45.2 mice were also crossed to B6,CD45.1 mice to generate a B10.A,CD45.1 strain [20]. To generate B10.A, mPCC(tg),CD45.1 mice, B10.A mPCC-transgenic, CD45.2 mice [19] were bred to B10.A,CD45.1. The IEk restricted MCC (Moth Cytochrome C)/PCC specific TCR transgenic 5C.C7 mice on Rag2−/−, CD45.1+/+, and CD45.2+/+ backgrounds have been previously described [5]. A1(M) mice originally from Steve Cobbold SAHA HDAC clinical trial [21] on a CBA/Ca background were backcrossed 11 times onto a B10.A,Rag2−/− background [14] and maintained by homozygous breeding. All animal protocols were as approved by the NIAID animal care and use committee. For adoptive cell transfers, cell suspensions from pooled lymph nodes of donor TCR-Tg Rag2−/− mice (>90% CD4+ T cells) were used without further enrichment and injected by the suborbital route. Acute antigen challenges were performed by intraperitoneal

injections of 30 μg of antigenic peptide (DbY or PCC; Anaspec or Bachem, USA) mixed with 5 μg of LPS (Sigma, MI, USA). T cells in transfer recipients were enumerated by isolating all lymph nodes and spleen, chopping them to approximately 1 mm cubes and digesting KU-57788 clinical trial with 2 mg/mL collagenase-D (Roche, USA) solution containing 3 mM CaCl2 in 1× PBS, at 37°C for 45 min. Digested tissue was dissociated using gentleMACS dissociator and gentleMACS dissociator C tubes (Miltenyi biotec, Germany) with manufacturer’s programmed settings m_Spleen 2.01 followed by m_Spleen 3.02 run serially on each sample. A total of www.selleck.co.jp/products/wnt-c59-c59.html 500 μL aliquots of the single cell suspensions were stained to obtain the percentage of CD4+ T cells and used to calculate the number of CD4+ T cells in each animal without any further manipulation. However, in order to track exceedingly low numbers

of transferred T cells, further enrichment was necessary. Following absolute counts, as stated above, as remaining cells were washed and centrifuged over Ficoll-Paque PLUS (GE Healthcare Bioscience) followed by enrichment for T cells by negative selection. Briefly, a cocktail of mouse and rat antibodies to B220 (RA3-6B2), CD11b (M1/770), I-EK (14.4.4s), CD8 (53-6.7), and MHC II (M5.114) (BD Bioscience) were used to label the cells and the bound fraction, pulled out using anti-mouse IgG and anti-rat IgG coated Dynabeads (Dynal Invitrogen). T cells were analyzed on a FACS Canto II cytometer (BD Immunocytometry) after staining with appropriate fluorophore coupled antibodies (Biolegend, Ebioscience or BD). We thank Eleanore Chuang for assistance with experiments, and Pascal Chappert for discussions. This research was supported by the Intramural Research Program of the NIH, NIAID.

In our search we found that the crude extract of the endophytic fungus UFMGCB 551 was able to inhibit several clinical strains of P. brasiliensis, and was also active in the bioautographic assay against Cladosporium sphaerospermum. The endophytic fungus UFMGCB 551 was isolated from the plant Piptadenia adiantoides J.F. Macbr (Fabaceae). The fungus was identified as Fusarium sp. based on its macro- and micro-morphology, and on the sequence of the internally

transcribed spacer regions (ITS) of its rRNA gene. The chromatographic fractionation of the fungal extract was guided by the bioautographic assay to afford three known trichothecene mycotoxins: T2-toxin (1) and a mixture of 8-n-butyrylneosolaniol (2) and 8-isobutyrylsolaniol (3). The learn more minimal inhibitory concentrations (MIC) of the these compounds against eleven clinical strains of P. brasiliensis were evaluated and found to be in the range between 75 and 640 nmol l−1 for 1 and 160–640 nmol l−1 for the mixture of 2 and 3. “
“The objective of this retrospective study was to evaluate results from voriconazole therapeutic drug MLN0128 molecular weight monitoring (TDM) in haematological patients in routine clinical practice. Between 2005 and 2010, 1228 blood samples were obtained from 264 haematological patients (median 3 samples/patient; range 1–27) receiving voriconazole for targeted/preemptive treatment of invasive aspergillosis (IA) (46.3%

of samples), empirical therapy (12.9%) or prophylaxis (40.8%). A high-pressure liquid chromatography assay was used to analyse voriconazole concentrations. Clinical and laboratory data were analysed retrospectively. The median of the detected voriconazole plasma concentration was 1.00 μg ml−1 (range <0.20–13.47 μg ml−1). Significant inter- and intra-patients variability of measured concentrations (81.9% and 50.5%) were identified. With the exception of omeprazole

administration, there was no relevant relationship between measured voriconazole concentrations and drug dose, route administration, age, gender, CYP2C19*2 genotype, gastrointestinal tract abnormality, administration via nasogastric tube, serum creatinine, and liver enzymes. However, per patient analysis identified significant role of individual Farnesyltransferase voriconazole dose and drug form change on measured plasma concentration. Measured voriconazole concentrations did not correlate with the treatment outcome of patients with IA. We only identified a limited number of adverse events related to voriconazole therapy; however, the median plasma concentration was not different from concentrations measured in samples without reported toxicity. Our retrospective study has suggested that routine monitoring of voriconazole plasma concentrations has probably only a limited role in daily haematological practice. “
“Treating patients with multiple oral leucoplakias (MOLs) who smoke is more difficult and complicated than treating those with single oral leucoplakia (SOL).

In the present work, we explore the role of Syk in antigen-induced FcεRI endocytosis, investigating, in particular, whether Syk kinase activity controls the covalent modifications of Hrs, the main Ub-binding adapter implicated in sorting of engaged FcεRI complexes to lysosome for degradation [11, 18]. By siRNA knock down of Syk, we initially

support our previous evidence that in RBL-2H3 cells Syk is required for efficient internalization of engaged FcεRI [10]. Our results are in agreement with previous studies reporting that in macrophages Syk plays a major role in FcγR-mediated phagocytosis [33, 34] and in B cells selleckchem is involved in both steady state and ligand-mediated BCR internalization [35]. However, our findings appear in contradiction with those of Bonnerot et al. [4] obtained using B lymphoma cells stably transfected with a chimeric receptor containing only FcεRI γ chain and of Kitaura et al. [36] showing that, in BMMCs, Syk has almost no effect on FcεRI endocytosis. A possible explanation for these contradictory findings is hat the contribution of Syk in regulating the internalization of γ chain containing receptors varies depending on receptor context (chimeric versus

endogenous multimeric receptor complex) and/or the source of cells used. Furthermore, Kitaura and coauthors [36] evaluated FcεRI internalization CH5424802 research buy only at 48 h after stimulation, leaving open the possibility that receptor internalization is affected at earlier time points. Our results, indeed, support a role for Syk in regulating mainly the early steps of antigen-induced FcεRI internalization: upon 30 min of stimulation almost 80% of the Syk knocked-down RBL-2H3

cells showed an impairment of FcεRI internalization, whereas upon 1 h of stimulation impaired FcεRI internalization was observed only in 50% of silenced cells analyzed. Thus, we would like to conclude that in mast cells Syk is required for a rapid and efficient antigen-induced FcεRI internalization, although PLEKHM2 we cannot rule out that redundant mechanisms of receptor entry may also exist. Notably, in agreement with previous findings [4, 8], our results demonstrate a critical role for Syk in controlling the fate of internalized receptor complexes: Syk knockdown prevents the sorting of internalized receptors into lysosomes for degradation. This result was somewhat expected in light of our previous finding that c-Cbl-mediated ubiquitination of engaged FcεRI complexes is dependent on Syk kinase activity [17]. Indeed, by controlling receptor ubiquitination, Syk might indirectly affect receptor trafficking. In this respect, we have recently demonstrated a key role for the Ub pathway to ensure proper endocytic trafficking of engaged FcεRI complexes to the lysosomal compartment where degradation of the complexes can take place [11]. In addition, Syk kinase activity might control the action of molecular adapters directly implicated in the endocytic pathway.

The virus was prevalent in more than 213 countries and caused IWR-1 in vivo at least 16,931 deaths (3). In Japan, the virus was first detected on 8 May 2009 at Narita airport in returnees from Canada; more than 20,000 confirmed cases and at least 99 deaths had been reported by 16 May 2010 (4). Although the A(H1N1)pdm09 has moderate virulence, it has mostly infected the young, especially those of school-age (5) and disproportionately impacted them (6). Pandemic (H1N1) 2009 virus is a novel reassortant, containing the PB1, PB2, PA, HA, NP and NS gene segments from North American triple-reassortant

swine viruses, and the NA and M gene segments from the Eurasian swine lineage (7). The latest whole-genome phylogenetic analysis of A(H1N1)pdm09 has shown

that at least seven different clades of viruses have been circulating globally (8). In this report, we analyzed the HA genes of 70 strains isolated from a single university population in order to describe the phylogenetic relationships of the strains circulating in the university. Nasal swab specimens from 71 patients, most of whom were current students and a few of Ivacaftor mouse whom were trainee doctors, were collected in the Dental and Medical Clinic attached to Health Sciences University of Hokkaido at Tobetsu in neighboring Sapporo. The Tobetsu campus, which is attended by approximately 2,500 students, consists of three faculties; Pharmaceutical Sciences, Dentistry, and Nursing and Social Services. Most of the students live in Tobetsu or commute from Sapporo on the same train line. The collected specimens were kept in a sample medium of DMEM supplemented with 1% BSA and 50 μg/mL gentamicin. The specimens were collected between 3 September and 15 December 2009, during which time the school was closed twice (from 21 to 23 October and 10 to 13 November) due to influenza epidemics (Fig. 1). All study patients tested positive for type A influenza by Meloxicam a rapid

test for influenza A and B viruses. The study was approved by the ethics committee of the Health Sciences University of Hokkaido and all patients gave informed consent. Madin-Darby canine kidney cells were cultured in DMEM supplemented with 10% FBS and 50 μg/mL gentamicin. The sample medium containing the specimen was clarified by centrifugation and inoculated into a monolayer of MDCK cells. After 1hr incubation at 35°C, the medium was removed and the cells were incubated in DMEM supplemented with 1% BSA, 50 μg/mL gentamicin and 5 μg/mL trypsin at 35°C for 2–3 days. When extensive cytopathic effects had been observed, the supernatants were collected, clarified and passaged once in MDCK cells. The HA genes of influenza A virus were amplified and analyzed as previously described (9). Briefly, 10 mL of the culture fluid of virus-infected cells was ultracentrifuged and the pellet was used for RNA extraction.

© 2011

Wiley-Liss, Inc. Microsurgery, 2011. “
“Perforator flaps as an innovative method for soft tissue transfer that maximizes Fludarabine function preservation, were originally introduced primarily as free flaps. Their reliability and versatility has been found to not differ from other sources of free flaps where total failure is an uncommon event. Partial failure should also be recognized as a possible dilemma that is perhaps more of a unique untoward sequela of perforator flaps. A retrospective review of our flap experience over the past decade included 310 perforator free flaps. Partial perforator flap failure that required a second free flap for salvage was selected in 6 patients. All perforator free flaps in our experience that had some form of partial failure were anterolateral thigh [ALT] free flaps. Clinically initially unrecognizable but ultimately distal flap ischemia could be attributed to poor flap design, and was the cause of immediate partial flap necrosis in 2 cases. Delayed difficulties were complications not specific to perforator flaps. In all cases, a free flap was considered the best option, and a second perforator free flap proved to resolve all reconstructive

objectives. The root cause of partial failure of a perforator free flap was found to be either iatrogenic or de novo in origin. The proper design requires an awareness of the correct topographic axis and an understanding of the perforasome concept to better insure adequate flap perfusion. If a free flap is still find more considered the best solution after a partial failure, the advantages and benefit of a second perforator free flap should not be overlooked. © 2013 Wiley Periodicals, Inc. Microsurgery 34:177–182, Sodium butyrate 2014. “
“Ultrasound (US) has been used in the management of carpal tunnel syndrome since the 1980s. The first report of US-guided carpal tunnel release (CTR) was published in 1997, with cadaver and clinical reports confirming the safe navigation of surgical tools

with US for division of the transverse carpal ligament. The MANOS CTR device was recently reported as a minimally invasive tool for CTR, and may be well suited for use with US guidance. The authors report three cases of US-guided CTR using the MANOS CTR device. The MANOS device was inserted in a blunt configuration into the safe zone, and the cutting surface was deployed with a thumb-activated trigger that simultaneously ejected a sharp through the palm. The transverse carpal ligament was divided safely and confirmed with US. US allowed for clear identification of the median nerve, safe zones, transverse carpal ligament, and the MANOS CTR device in relation to all pertinent structures of the carpal tunnel. Complete division of the transverse carpal ligament was confirmed in all three cases.

Nuclear extracts from Jurkat cells were used as negative control, and nuclear extracts from

Raji cells included in the kit and from MoT cells served as positive controls in the assay. In order to address the potential cytotoxic effects of signaling pathway pyrrolidine dithiocarbamate (PDTC) on mononuclear cells, experiments were performed treating PBMCs with PDTC for 1 h at three different concentrations (1 μM, 10 μM, 30 μM) or left them untreated, then washed three times with RPMIc. After 3 h in culture, cell viability was measured by the trypan blue exclusion method. PDTC-treated cells were also subjected to apoptosis determination by fluorescence activated cell sorter (FACS) using the annexin-V/7-aminoactinomycin D (7AAD) kit (BD Bioscience Pharmingen). More than 95% viable cells were determined in trypan blue exclusion assay for PBMCs treated with PDTC under these concentrations. In addition, the PDTC agent did not affect the viability of the cells as assessed by annexin-V and 7AAD staining (data not shown), and therefore pretreatment of PBMCs was performed with 30 μM of PDTC. To examine the role of NF-κB in Tax-mediated CC-chemokine secretion, PBMCs were pretreated with 30 μM of PDTC, a potent inhibitor of NF-κB, for 1 h then washed three times with RPMIc, followed by

treatment with Tax proteins (100 pM) for 3 h, shown to be the optimal time-point to assess levels of CC-chemokines in Tax-treated PBMCs (Fig. 1). In other experiments, see more PBMCs were transduced with the NF-κB super-repressor (NF-κB/SR) at an MOI of 25 using lipofectamine plus reagent (Invitrogen) for 20 h prior to Tax protein treatment (3 h). PBMCs were also co-transduced with NF-κB/SR and Ad-Tax2 or Ad-GFP. Cell-free supernatants were harvested after 24 h of incubation and assayed for MIP-1α, MIP-1β and RANTES expression, as described above. All statistical analyses were performed using GraphPad Prism version 6·00 for Windows (GraphPad

GNA12 Software http://www.graphpad.com) and the data expressed as mean ± standard error of the mean. One-way analysis of variance (anova) with Bonferroni’s multiple post-test comparison were used to evaluate three or more groups. Statistical comparisons for two groups were assessed by two samples assuming equal variances Student’s t-test. P-values <0·05 were considered statistically significant. We have reported recently that extracellular Tax2 and Tax1 proteins induced high levels of CC-chemokines in mononuclear cells [24, 25]. The optimal dose of protein required to detect CC-chemokine secretion was determined previously by exposing PBMCs to increased concentrations of Tax proteins [24]; the concentration of 100 pM was optimal, and therefore used in all subsequent experiments. In order to determine the time of MIP-1α, MIP-1β and RANTES release, PBMCs were treated once with Tax2A (subtype A), Tax1 or mock-treated control and then cell-free supernatants were harvested after 1, 2, 3, 6, 12 or 24 h of incubation.

In MS, the precise distribution of different laminin isoforms is reported to be important for integrin-mediated leucocyte extravasation to the active lesion, where ‘perivascular cuffs’ of inflammatory infiltrates

specifically associate with patches of laminin α4 but not laminin α5 expression [347,348]. In the chronic lesion, increased perivascular expression of fibrillar collagens (types I, III and V) and the SLRPs decorin and biglycan was suggested to reduce monocytic expression of the leucocyte attractant chemokine CCL2 (MCP1) [349]. Similarly to the approaches discussed earlier with regards to traumatic CNS injury, manipulating the https://www.selleckchem.com/autophagy.html ECM therefore a represents a potential therapeutic strategy to overcome www.selleckchem.com/products/abc294640.html demyelination (recently reviewed in [350]). Indeed, reduction of CSPG synthesis using xyloside, in vivo, was shown to increase OPC and oligodendrocyte numbers in lesions and improve remyelination in a lysolecithin murine model [351]. Thus, there is promise for future studies to apply ECM modification strategies to models

of MS and it will be of great interest to determine whether these strategies can improve disease pathology and lead to functional repair. The ECM plays a critical role during development and following disease or injury to the CNS. Rather than mere provision of a supportive

environment, the ECM is actively involved in many fundamental processes such as cell signalling, axon guidance and synaptic plasticity. Following disease or damage to the CNS, the composition Enzalutamide chemical structure of the ECM can prove detrimental to axonal regeneration, plasticity and repair. Manipulating the ECM represents a powerful therapeutic approach, with the aim of recapitulating beneficial processes that occur during development and/or reducing negative remodelling after injury, either by targeting specific ECM components or by global targeting of families of ECM molecules. There is now much pre-clinical evidence to suggest that beneficial outcomes can be achieved following traumatic brain and spinal cord injury with therapies involving matrix manipulation and encouragingly, some of these strategies are progressing closer to clinical application. We may only be beginning to understand the complexities of ECM interactions in neurodegenerative disorders but it appears that manipulations of the ECM may well have wide applications in future strategies to promote repair following CNS injury or disease. “
“F. Mori, K. Tanji, Y. Miki, A. Kakita, H. Takahashi and K.

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 find more 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 selleck screening library 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 next 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.