We showed here characteristic four patients of MCD with kidney involvement. Various humoral factors, which might be associated with activated cells in MCD, could be involved in the pathogenesis of MCD-related kidney diseases. KOSURU SRINIVAS1, NAGARAJU SHANKAR PRASAD1, PARTHASARATHY RAJEEVALOCHANA1, BAIRY MANOHAR1, ATTUR RAVINDRA PRABHU1, GUDDATTU VASUDEVA2 1Department of Nephrology, Kasturba Medical College, Manipal University, Manipal;

2Department of Statistics, Manipal University, Manipal Introduction: Accurate assessment of donor kidney function is pivotal in live kidney transplantation. Currently 99mTc-diethylenetriaminepentaaceticacid (DTPA) based measured GFR is the gold standard but it is complex and expensive. Though various creatinine based GFR estimation equations Y-27632 nmr are in use,

none of them have been validated in Indian population. The objective of this study is to assess whether these equations are accurate and reliable for evaluation of donor kidney function. Methods: Fifty-two consecutive renal donors who had undergone 99mTc-DTPA GFR estimation were included after institutional ethical committee Raf inhibition clearance. The predictive capabilities of the Cockcroft and Gault equation corrected for body surface area (CG-BSA), modification of diet in renal disease (MDRD) four and six variable equations, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation and 24-hr urinary creatinine clearance (urine-CrCl) corrected for BSA were compared with measured GFR (DTPA). Data was analyzed using SPSS version15. Results: The mean age of the study group was 42.7 ± 9.7 years and 82.7% were female. The mean measured DTPA GFR was 90.69 ± 14.13 ml/min/ 1.73 m2. The bias, precision

Acyl CoA dehydrogenase and accuracy of all equations were calculated in comparison with measured GFR (Table 1). In our study, MDRD 6 equation showed highest precision (Lowest SD of mean bias) among the five equations. The accuracy within 30% was highest for MDRD 6 (88.50%) followed by CKD-EPI (82.70%). The least precision and accuracy was seen with urine-CrCl. Conclusion: Of all the estimation equations, MDRD six variable is the most precise and accurate. However, poor correlation of these equations with measured GFR makes them suboptimal for donor evaluation. KUMAR VIVEK1, AHLAWAT RAVINDER2, SHARMA R K2, GUPTA A K2, MINZ M3, JHA VIVEKANAND1 1Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India; 2Department of Hospital Administration, Postgraduate Institute of Medical Education and Research, Chandigarh, India; 3Department of Renal Transplant Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India Introduction: Deceased donor organ program is still in infancy in India.

The results demonstrated significant differences in selected serum inflammatory mediators during the ligation phase of the study related to the time-point NSC 683864 clinical trial of the study and associated with ligation of teeth in two quadrants (MP) or four quadrants (D). Interestingly, the profile of inflammatory mediators at the various time-points of disease was not associated consistently with increasing disease, with only IL-6 levels demonstrating a significant increase after 6 months of periodontal disease. The results suggested that although there were variations in systemic analyte measures related to periodontitis, individual

variation in the clinical responses of the animals may have a substantial impact upon interpreting the direct link between oral disease and systemic responses. check details Moreover, while previous studies in human periodontitis have suggested local involvement of a range of mediators, including IL-1β and TNF-α, expression of these proinflammatory response molecules were not observed in the systemic responses of the baboons to periodontal disease progression. This is consistent with differences in local versus systemic cytokine/chemokine response profiles observed with this disease in humans [13]. Therefore, we evaluated changes in the inflammatory mediators through the 6-month ligation in subsets of the animals based upon clinical presentation

at baseline. These results demonstrated consistent patterns of systemic

inflammation related to progressing periodontitis. PGE2 levels increased significantly by MP and remained elevated throughout the entire pregnancy. Similarly, BPI levels were also increased significantly by MP in most of the animals and generally decreased substantially by delivery. LBP levels were elevated generally at baseline and decreased significantly throughout the disease process. As was noted with the population as a whole, IL-6 levels were increased significantly by delivery, irrespective of the baseline clinical characteristics of the animals. Both IL-8 and Rho MCP-1 decreased from baseline throughout the study, with the lowest levels of IL-8 in serum samples obtained at delivery, unrelated to the clinical presentation of the animals at baseline. A summary of these outcomes was that the clinical presentation at baseline had less impact on the systemic inflammatory mediator levels than the effect of the continued disease over 6 months induced by ligation and creation of chronic periodontitis in the animals. Finally, based upon these findings, we evaluated response differences in subsets of animals as they progressed through the experimental challenge during pregnancy. Thus, at baseline, stratification of the animals related to naturally occurring oral health/disease showed some distinct differences in serum inflammatory mediators that differentiated the healthy from gingivitis from the periodontitis groups.

Generally, spleen cells were obtained at the time of

BALF collection from experimental HP mice. CD4+ T-cell purification and staining with PKH67 were performed according to the manufacturer’s protocol (Sigma). Pre-stained CD4+ T cells were diluted (BALF cells: T cells) 1:6 or 1:12, then co-cultured for 3 days. A T-cell proliferation index was evaluated by measuring the decreasing PKH67 staining intensities in CD4+ T cells after co-culture with BALF cells. For in vitro experiments, the effects of CD11b+Ly-6Chigh or CD11b+Ly-6C− cells on T-cell proliferation were assessed using [3H] thymidine as described previously 11. In brief, U-bottom 96-well plates were coated with anti-CD3/CD28 antibodies (1 μg/mL each) Cabozantinib ic50 overnight at 4°C. CD4+ T cells (0.3×105 cells/well) were

purified using specific MACS beads (Miltenyi Biotec) and then cultured with plate-bound anti-CD3/CD28 for 3 days. The activated CD4+ T cells were co-cultured with BM cell-derived CD11b+Ly-6Chigh, CD11b+Ly-6Cint, and CD11b+Ly-6C− cells from the beginning of the culture. During the final 16 h of the 3-day culture, 1 μCi [3H] thymidine was added, and the ZD1839 concentration cells were then harvested. The supernatants (50 μL) were harvested before addition of [3H] thymidine to measure cytokine levels. For statistical comparisons, non-parametric two-tailed Mann–Whitney U-tests and two-way ANOVA were used. All statistical analyses were performed with Prism 4 software (GraphPad Software, La Jolla, CA, USA). We thank Ms. Masako Seki, Ms. Kanako Ito, Ms. Megumi Nagayama and Mr. Tetsuya Shiota (GalPharma, Japan) for technical from assistances and Dr. Aya Yokota (Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Japan) for technical assistance with cell sorting. This work was supported, in part, by a Grant-In-Aid for young scientists (B) 2008-2009 (20790570) to T. A. from the Japan Society for Promotion of Science (JSPS), by Kagawa University Characteristic Prior Research Fund 2009 to M. H., and by grants from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.

Conflict of interest: The authors declare no financial or commercial conflict of interest. “
“Invariant NKT (iNKT)-cell stimulation with exogenous specific ligands prevents the development of type 1 diabetes (T1D) in NOD mice. Studies based on anti-islet T-cell transfer showed that iNKT cells prevent the differentiation of these T cells into effector T cells in the pancreatic lymph nodes (PLNs). We hypothesize that this defective priming could be explained by the ability of iNKT cells to induce tolerogenic dendritic cells (DCs) in the PLNs. We evaluated the effect of iNKT-cell stimulation on T1D development by transferring naïve diabetogenic BDC2.5 T cells into proinsulin 2−/− NOD mice treated with a long-lasting α-galactosylceramide regimen.

8 years (ranging 2.4–6.6 years). The preoperative Harris Hip score (HHS) in the patients with arterial blood supply insufficiency was 48.18 ± 7.81 and the postoperative HHS was 93.27 ± 3.03. The preoperative HHS in the patients with venous stasis was 44.04 ± 6.40, and the postoperative HHS 92.65 ± 2.93. The postoperative DSA showed an improved perfusion of the femoral

head in 44 hips. Our experience showed that DSA would help to select the appropriate procedure for treatment of ONFH in the early stage. © 2013 Wiley Periodicals, Inc. Microsurgery 33:656–659, 2013. “
“The correlation between calcium ion (Ca2+) concentration and electrophysiological Maraviroc recovery in crushed peripheral nerves has not been studied. Observing and quantifying the Ca2+ intensity in live normal and crushed peripheral nerves was performed using a novel microfine tearing technique and Calcium Green-1 Acetoxymethyl ester stain, a fluorescent Ca2+ indicator. Ca2+ was shown to be homogeneously distributed in the myelinated sheaths. After a crush

PD332991 injury, there was significant stasis in the injured zone and the portion distal to the injury. The Ca2+ has been almost completely absorbed after 24 weeks in the injured nerve to be similar to the controls. The process of the calcium absorption was correlated with the Compound Muscle Action Potential recovery process of the injured nerves. This correlation was statistically significant (r = −0.81, P < 0.05). The better understanding of this process will help us to improve

nerve regeneration after peripheral nerve injury. © 2009 Wiley-Liss, Inc. Microsurgery, 2010. “
“Rodent models are used extensively for studying nerve regeneration, but little is known about how sprouting and pruning influence peripheral nerve fiber counts and motor neuron pools. The purpose of this study was to identify fluctuations in nerve regeneration and neuronal survival over time. One hundred and forty-four Lewis rats were randomized to end-to-end repair or nerve grafting (1.5 cm graft) after sciatic nerve transection. Quantitative histomorphometry and retrograde labeling of motor neurons were performed at 1, 3, 6, 9, 12, and 24 months and selleck inhibitor supplemented by electron microscopy. Fiber counts and motor neuron counts increased between 1 and 3 months, followed by plateau. End-to-end repair resulted in persistently higher fiber counts compared to the grafting for all time points (P < 0.05). Percent neural tissue and myelin width increased with time while fibrin debris dissipated. In conclusion, these data detail the natural history of regeneration and demonstrate that overall fiber counts may remain stable despite pruning. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012. "
“Complete loss of free latissimus dorsi muscle flaps to the leg is frequently reported. The purpose of this study is to analyze the outcome of latissimus dorsi muscle flaps to the lower extremity in children. Patients and methods.

Rutgers et al. [33] demonstrated that changes in BALF do not reflect changes in the lung tissue. Because airway inflammation was induced in all age groups by i.n. sensitization with OVA in adjuvant followed by OVA challenges, our study suggests that differences in BALF

and tissue inflammation may be influenced by age. The percentage of PAS staining cells was affected by age in the same way as epithelial DAPT cell shedding (as observed in BALF) and, thus, suggests that the pulmonary epithelium is actively involved in the allergic airway response in the i.n. model. In the i.p. model, the largest epithelial shedding was also observed in 6-week-old mice. Our study was designed to cover an age span which is usually

employed in Caspase-independent apoptosis experimental research. The largest differences for both models were between the 1-week-old mice and the older mice. However, the allergic response continued to change also from 6 to 20 weeks of age in the i.n. model. Other studies based on i.p. sensitization demonstrate both decreases [21] and increases [20, 24, 34] in IgE and airway inflammation within the age span investigated here. IFNγ has been described to increase with age, while TH2 cytokine responses decreased [20, 21], but we found no such pattern for IFNγ (Table 3). The published studies used BALB/c or C57Bl/6 mice, which may differ immunologically from the NIH/OlaHsd strain. We have previously shown that the NIH/OlaHsd strain is a good IgE producer [35, 36] and that the 10 μg OVA i.p. immunization produces comparable IgE and IgG1 patterns in the NIH/OlaHsd, BALB/cJ and C57Bl/6 strains although the antibody levels were higher in the NIH/OlaHsd strain (unpublished data). Although the observed sex differences in the NIH/OlaHsd strain

were comparable to those of the BALB/c and C57Bl/6 strains (see above and unpublished data), it is possible that strain differences may explain the discrepant observations on age. However, from our study, it must be concluded that the influence of age on specific IgE and allergy outcomes in two different Phospholipase D1 mouse models is highly dependent on immunization dose and route (Table 3). TH17 activity is generally associated with neutrophil and eosinophil inflammation in allergy [37, 38], but IL-17 has also been observed to downregulate pulmonary eosinophil recruitment during an active allergic response [39]. It was previously reported that following airway sensitization, cytokine production was low in SLNs in contrast to MLNs [40, 41]. Except for IL-17A, the same was observed in the present study. Further, we observed that MLN but not SLN cell numbers were affected by immunization with adjuvant. De Haar et al. [42] found that T cells from SLNs in contrast to lung-draining lymph nodes do not proliferate following i.n. sensitization with OVA and adjuvant.

5A and data not shown). However, a decrease in CXCR3 surface expression was observed. NK cells did not proliferate, displayed no change in GrzB levels and were unable to lyse K562 cells in response to LASV- and MOPV-infected MΦs (data not shown). NK-cell activation is triggered by some NK-cell surface molecules and receptors. The blockade of CD40L, NKG2D, NKp30, NKp44, or NKp46 with neutralizing Ab had no effect on the expression of NK-cell surface

molecules (data not shown). We show here that cell contacts between NK cells and infected MΦs are essential for activation of NK cells and increase cytotoxicity while they do not seem to be involved in the modulation of CXCR3 expression. We previously showed that LDK378 MΦs secrete type I IFNs in response to MOPV infection, but that only low levels of these compounds

are produced during LASV infection. CXCL9, CXCL10, and CXCL11 are secreted in response to type I and II IFNs and bind CXCR3. The presence of type I IFN and CXC chemokines was analyzed in the supernatants of NK/MΦ cocultures. In cocultures HIF inhibitor review with NK cells, MOPV-, and to a lesser extent LASV-, infected MΦs secreted significant amounts of type I IFN and CXCL11 (Fig. 5B). Neutralizing mAbs directed against IFN-R and IFNα were used to inhibit type I IFN, and NK-cell stimulation by CXCL9, CXCL10, and CXCL11 was prevented with neutralizing mAbs directed against CXCR3 or CXC chemokines themselves. Our experiments with an irrelevant Ab gave results similar to those reported in Fig. 2. The inhibition of type I IFN reduced the increase in CD69 and NKp30 expression (Fig. 5C). However, neutralizing mAbs against type I IFN induced a decrease

in CXCR3 surface expression, although this decrease was smaller than that obtained with the irrelevant Ab. Moreover, we observed a global increase in CXCR3 expression (Fig. 5C). NK-cell proliferation Megestrol Acetate and the intracellular GrzB expression induced by LASV- and MOPV-infected MΦs were also abolished by the blockade of type I IFN (data not shown). After CXCR3 neutralization, NK cells remained activated in terms of the upregulation of CD69 and NKp30, proliferation and enhanced GrzB expression (data not shown). Neutralizing mAbs against CXC chemokines gave similar results. In addition, they induced a decrease in CXCR3 surface expression, but smaller than that obtained with the irrelevant Ab. Thus, our findings demonstrate that the type I IFN secreted by MΦs are necessary for NK-cell activation during LASV and MOPV infection but CXC chemokines have minor effects. We developed a model of NK cells cocultured with infected APCs, for studies of the role of NK cells and the importance of interactions during LASV and MOPV infections. We used LPS-activated APCs as a positive control for the APC-mediated activation of NK cells. We confirmed that LPS did not activate NK cells directly (data not shown).

2A) and primary human T cells (Supporting Information Fig. 3A). TPEN potentially even slightly increased STAT5 phosphorylation in response to IL-2. In addition, treatment with zinc and pyrithione had no impact on STAT5-phosphorylation (Fig. 2A). It is important to consider that TPEN may not click here only chelate free zinc, but also interact with tightly protein bound zinc, such as in zinc fingers. This has recently been investigated

in vitro by monitoring the DNA-binding capacity of the Zn3-SP1 zinc finger transcription factor. TPEN removed zinc from zinc fingers in vitro, whereas incubation of LLCPK1 cells with 100 μM for 30 min had no effect on DNA-binding of Zn3-SP1. Even after 24 h, 30 μM TPEN were required to affect DNA binding 24. Consequently, the conditions used in our experiments are significantly lower than the ones shown to interfere with tightly protein bound zinc. In

light of the differential role of free zinc in ERK and STAT5 activation, an effect on IL-2R tyrosine phosphorylation seems unlikely as a mechanistic explanation, because it should affect both pathways in a similar manner. ERK is activated via a cascade originating from Tyr338 on the IL-2R β chain via the Shc/Grb2/SOS/Ras/Raf/MEK/ERK pathway 10. TPEN had no effect on the IL-2-induced activating phosphorylation of Raf on serine 338 (Fig. 2B). These results were confirmed in primary T cells, where TPEN had no effect on IL-2-induced Raf phosphorylation, but inhibited MEK1/2 and ERK1/2 phosphorylation in a concentration-dependent manner (Supporting Information Fig. 3A). This indicates that zinc signals regulate ERK signaling MLN8237 nmr downstream of Raf. Several members of the DUSP family and PP2A dephosphorylate ERK 13, and both types of phosphatases are inhibited by zinc 25–27. Therefore, we performed an assay to measure the impact of zinc on total phosphatase activity (Fig. 2C). There was a clear, concentration-dependent effect of zinc, but it Calpain was observed at significantly higher (micromolar)

concentrations than the nanomolar amounts found in intact cells (Supporting Information Fig. 1C). However, when free zinc in the lysate was measured with FluoZin-3, we found that the lysate buffers zinc by more than three orders of magnitude, resulting in concentrations in the nanomolar range (Fig. 2D). When these actual concentrations are considered, phosphatase inhibition is observed at physiologically relevant concentrations of free zinc (Fig. 2E). Next, we used an in vitro dephosphorylation assay to investigate the impact of zinc on MEK and ERK phosphorylation, showing that zinc protected both kinases from dephosphorylation (Fig. 2F). Notably, the effect on ERK was observed in the presence of the MEK inhibitor U0126, demonstrating that it was not simply a result of preserved MEK activity, but that dephosphorylation of both kinases was inhibited by zinc.

Serum MMCP-1 has been shown to be a marker for

mucosal mastocytosis and increased gut permeability [32] as well as for mast cell dependent intestinal inflammation [33]. A strong correlation between anaphylactic score and levels of MMCP-1 was found. However, cross-allergy did not reveal any signs of mast cell activation, as the levels of MMCP-1 in animals challenged with cross-reactive legumes were comparable with the levels of immunized, not challenged animals. This suggests selleck screening library that intestinal mast cells are less activated in the cross-allergic reactions observed. It has been reported that food induced anaphylaxis may depend more on macrophages and basophils than on mast cells [34], and more studies are needed to elucidate the roles of macrophages and basophils in cross-allergy. That no cross-reactivity could be observed in the PCA-test may also support the notion that cross-allergic reactions are not mediated through a mast cell dependent pathway. However, because of the functionality of the test, it could also be a reflection of the difference in affinity between epitopes. Two distinct mechanisms have been reported to induce systemic anaphylaxis in the mouse [35]. The classical pathway is mediated by allergen cross linking of IgE bound to the high affinity receptor (FcεRI) on mast cells. The alternative

pathway is thought to involve macrophages, FcγRIII, IgG antibodies and platelet activating factor [36]. A partial inhibition Tau-protein kinase of lupin specific IgG1 by peanut and soy and of fenugreek specific IgG1 by peanut was observed. A role for both IgE and Selleck Pexidartinib IgG1 in the cross-allergic responses in mice is therefore possible. Several studies have implied that both the classical and the alternative pathway of food induced anaphylaxis are involved simultaneously in mice, and that abrogation of one pathway only partially abrogates anaphylactic responses [37–39]. Tsujimura

et al. [40] demonstrated that basophils play a crucial role in IgG mediated anaphylaxis in their mouse model. It has also been reported that mast cells contribute to anaphylaxis through both IgE and IgG1, whereas macrophages contribute through IgG1 exclusively. The role of IgG1 in anaphylactic reactions in mice complicates the extrapolation of findings from mouse to man, as IgG-mediated anaphylaxis to food has not yet been described in man. The relevance to human anaphylaxis of the different pathways observed in mice needs to be investigated. Strait et al. have shown that although the IgE pathway is more sensitive and requires lower threshold levels of antigen for full activation, IgG mediated responses can also be severe [36, 41]. Our studies support the involvement of IgG1 in cross-allergy, while we were unable to confirm the involvement of IgE and mast cells.

[53] In vivo, newly generated peripherally find more induced Treg cells (within their first week) retain some plasticity (~ 50% maintain FOXP3 expression) whereas mature peripherally induced Treg cells achieve remarkable stability (~ 99%),[54] through mechanisms also involving CpG demethylation and autoregulation.[45] Hence, the plasticity and stability

phenotypes of distinct CD4 T-cell subsets are varied and developmentally regulated, and are controlled by transcriptional and epigenetic mechanisms. Several recent studies described here detail the relative roles and co-operative function of transcription factors in the initiation of T-cell subset differentiation and provide consensus on a primary role for ERFs in the early activation of enhancers and see more associated gene transcription. Indeed, with MRFs dispensable for much of the early Th cell transcriptional programme, and their relatively small regulatory footprint, some may see fit to question their ‘master’ status. However, while the in vitro studies are detailed and incisive in their control over comparative

conditions, it is crucial to consider what we have learned from in vivo loss-of-function studies, and to appreciate the function of MRFs in heritable maintenance of cellular phenotype, environmental responsiveness and plasticity (see above), as well as the complexity of Th cell phenotypic delineation in the organism. The role of FOXP3 in Treg cell biology illustrates this distinction in perspective well. Stimulation of naive CD4 T-cells through the TCR, together with environmental sensing of TGF-β and IL-2 can recapitulate a significant fraction of the Treg cell transcriptional signature, independent of Foxp3 expression.[35, 55] Perhaps this is analogous to the minor role for TBET, GATA3 and RORγt in initializing Th1, Th2 and Th17 enhancer activation and transcriptional signatures. However, in vivo, FOXP3 is critical for Treg cell identity and loss of Foxp3 in mature Treg cells results in their dedifferentiation, acquisition of alternative T-cell subset phenotype,

extensive immunopathologies and old death.[29, 56] Although we can appreciate the major role of ERFs in the initial differentiation process and the mechanistic insights gained from these studies, we can also acknowledge that the transcriptional programmes they induce are insufficient for complete in vivo, faithful, CD4 T-cell subset commitment and maintenance. As quantitatively inferior as their roles may seem in the initialization of enhancers and transcriptional programmes, minute features such as modulation of a key set of genes or establishment of stabilizing positive feedback loops, establish MRFs as central and defining factors in CD4 T-cell subsets. Studies of mechanisms employed by MRFs to orchestrate these cellular phenotypes are important for a general understanding of cellular differentiation and identity.

By contrast, on Ag-experienced CD8+ T cells we found that whereas IFN-α enhances the effector functions, it decreases fold cell expansion. No differences were found between IFN-α2b and IFN-α5 subtypes, suggesting redundancy in the system. The magnitude of the stimuli and

the inputs from different stimulatory/inhibitory receptors are critical parameters for the outcome of the T-cell response. Thus, the need of choosing a fixed dose of stimuli, a single costimulatory signal and few time points for the array analyses provides a limited and static picture of the transcriptional changes induced on human T cells. Despite this limitation, our array data provided a baseline definition of the IFN-α transcriptional effects on human CD8+ Fulvestrant T cells and will form the basis for further and more detailed studies. The results of the transcriptional analysis of human CD8+ T cells stimulated with IFN-α alone agree with previous studies of IFN-α stimulation of unfractionated PBL 18, 19. The overall similarity suggests that IFN-α imprints a common transcriptional

signature on the peripheral blood immune cell populations. Despite induction of relevant genes for effector functions, human CD8+ T cells treated only with IFN-α experienced no sign of activation. However IFN-α-derived signals synergize with signals elicited by CD3/CD28-triggering and promote the acquisition of effector functions on human CD8+ T cells. The biological meaning of the regulation of all these genes relevant for CD8+ T-cell functions by IFN-α itself

is still unknown. One possibility is that pre-exposure to IFN-α induces mRNA Anacetrapib that facilitate T-cell activation selleck chemical upon an eventual Ag encounter. Transcriptional analyses performed in human CD8+CD45RO− cells stimulated with Beads and either IFN-α2b and/or IFN-α5 show that, as a signal-3 cytokine, IFN-α regulates outstanding genes involved in the overall activation of T cells. Among these genes we found IL2. IL-2 is an important cytokine for survival, clonal expansion and differentiation of T cells 20. The fact that IFN-α also promotes the surface expression of CD25 strengthens the idea that IFN-α may promote the CD8+ T-cell response, at least in part, by inducing additional cytokines that could further stimulate CD8+ T cells in an autocrine manner. Importantly, the chief transcriptional signature of IFN-α, as a third signal, encompasses the up-regulation of transcripts involved in effector functions (IFNG, GZB and TRAIL) as well as production of chemokines (CXCL10 and CXCL11). A similar transcriptional signature has been found in OT1 cells stimulated in vitro with artificial DC and IFN-α 14, suggesting that IFN-α may promote the conversion of CD8+ T cells not only into highly effector cells but also into efficient chemotactic attractants of additional effector cells. This transcriptional effect was substantiated at the protein level and verified by functional assays.