Analyses of tumour-infiltrating lymphocytes revealed a greater percentage of Treg in HNSCC compared with the circulating counterpart of both patient and healthy controls [12], suggesting that in HNSCC Treg cells are recruited in the tumour area respect to the lymphnode or circulating location. Recently, it has been reported that naïve antigen-specific T cells can be either activated or tolerized simultaneously in the same host, depending on the microenvironment in which the epitope is presented [13]. Effector T cells generated in lymph nodes

are tolerized rapidly when they infiltrate antigen-expressing Emricasan research buy tumour tissues. Interestingly, tolerant T cells persist only in the tumours and resemble tumour infiltrating lymphocytes seen in cancer

patients [14]. In the clinical setting the effect of Treg may be attenuated by depleting them with non-myeloablative chemotherapy or monoclonal antibodies against inhibitory receptors (anti-CTL antigen-4 [CTLA4]) [15, 16]. In various mouse models antibodies against the glucocorticoid-induced tumour necrosis factor receptor family (GITR) are able to downregulate Treg functions increasing the efficacy of immunotherapies [17, 18] Brigatinib solubility dmso However the role of the human counterpart of this receptor huGITR appears to be quite different with less activity on Treg suppression [19, 20] Controlled and effective modulation of Treg Doramapimod clinical trial cell function for cancer therapeutics will be contingent on a better understanding of the molecular basis of Treg cell interaction with tumour cells and ensuing immunosuppressive mechanisms. A study using a synthetic monoclonal antibody targeted against CD28 met with disastrous results, reminding us that manipulation of costimulatory/regulatory pathways requires more information in this field [21]. Nevertheless continuing investigation on the biology of Treg in antitumour immunity Rebamipide and potential toxicities of Treg suppression will undoubtedly implement the efficacy of cancer immunotherapies. Finally in patients with HNSCC the absolute number of T-lymphocytes

both CD4+ and CD8+ is reduced and it may be related with a decrease expression of chemokine receptor 7 (CCR7) on T cells [22]. CCR7 has been implicated in protecting CD8+ T cells from apoptotic cell death. Indeed CD8+ CCR7-negative T lymphocytes that are more sensitive to apoptosis were increased in HNSCC patient peripheral blood compared with healthy controls [22]. These are the major barriers that have to be broken by an effective therapeutic vaccine. Before reaching the tolerance or tumour escape a therapeutic vaccine must elicit a strong cellular immune response involving the CD4 and CD8 stimulation. Many strategies have been developed to induce a response against the TAA. In particular the HPV E7 antigen has been utilised to develop an incredible large number of different possible therapeutic vaccines extensively reviewed elsewhere [6].

There is a discontinuous narrow coastal terrace, on which most development has occurred (Fig. 8b), and a fringing reef with a number of reef-gap beaches. In addition to coastal hazards, rockfall and landslides are a threat to development on the WZB117 cost coastal learn more terrace beneath

steep slopes. Fig. 8 a Reef-fronted beach with outcrop of granite and beachrock (foreground), east coast of high island of Mahé, Seychelles (photo DLF 2005). Note hotel overhanging seawall and beach. b Development on coastal terrace, Baie de la Mouche, west coast of Mahé, where natural berm has been removed for road construction: tsunami damage occurred here in 2004 (photo DLF 2005) Coastal hazards on small islands The selleck screening library nature of the hazards, exposure and vulnerability—thus the most relevant adaptation measures—vary between island types in relation to elevation, but also to size, topography, bathymetry, lithology, reef morphology and ecological integrity, as well as human factors such

as shore protection, or location and design of critical infrastructure and other property. The geographic region is important as it determines ocean climate (e.g., temperature and coral growth rate), storm climatology (including wind and wave patterns), and the regional trend of sea-level rise. Islands within ± 5° latitude about the equator are generally free of tropical cyclones, but occasional storm incursions, exceptional PD184352 (CI-1040) winds, or impacts of far-travelled swell from mid-latitude storms can cause significant damage, the effects of which are also influenced by sea-level variability resulting from El Niño-southern oscillation (ENSO) or other large-scale climate cycles. At tropical to mid-latitudes >5° (north or south),

tropical cyclones are a major recurring threat (Hay and Mimura 2010). In addition to climate effects, geophysical hazards such as volcanic eruptions, landslides, earthquakes and tsunami require attention and may pose equal or greater risks to island communities. Apart from catastrophic events, coastal stability is a function of wave energy, erodibility, and sediment supply, which may depend on reef health and the production of biogenic sand (Kench and Cowell 2001; Perry et al. 2008, 2011). Reefs represent not only a source of sediment, but play a major protective role, absorbing much of the deep-water wave energy. There is cause for concern about the mid-term fate of coral reefs (e.g., Hoegh-Guldberg et al. 2007), but recent work has shown that the coralline algae forming the resistant rims of some reefs may be more resistant to acidification than previously thought (Nash et al. 2013). In some places, exposure is mitigated and resistance to erosion increased where mangroves are present along the shore. Removal of mangroves can often be identified as a source of erosion problems in coastal communities (Mimura and Nunn 1998; Solomon and Forbes 1999).

Figure 2 High-resolution transmission electron micrographs and selected area electron diffraction patterns. (a) Cross-sectional high-resolution transmission electron micrograph of the EuTiO3/SrTiO3(001) interface along the SrTiO3[ ] zone axis. The insets

show the high-resolution micrographs of the EuTiO3 films and SrTiO3 substrate taken in focus, respectively. Selected area electron diffraction patterns of (b) EuTiO3 learn more and (c) SrTiO3, respectively. To investigate the crystallographic uniformity of this epitaxial growth, the EuTiO3/SrTiO3(001) structure was assessed by HRXRD. Both EuTiO3 and SrTiO3 were reported to have the cubic perovskite crystal structure at room temperature and have a lattice constant of 0.3905 nm [21], indicating zero lattice mismatch between EuTiO3 and SrTiO3. Figure 3a shows symmetric HRXRD longitudinal ω- 2θ scans taken within a 2θ range from 10° to 110° for the as-grown and postannealed samples. Apart from the (00l) (l = 1, 2, 3, and 4) reflections of SrTiO3, the (00l) reflections of EuTiO3 for the as-grown sample can be identified and no reflections pertinent to a secondary phase can

be found, indicating that the epitaxial growth of EuTiO3 is oriented along the c-axis. The out-of-plane lattice constant of the as-grown films calculated from the (001), (002), and (004) peaks are 0.3789, 0.3821, and 0.3831 nm, respectively. They are much smaller than the reported value of 0.3905 nm for bulk EuTiO3[22, 23] and show an out-of-plane lattice shrinkage of 2.9%, 2.1%, and 1.9%, respectively. selleck screening library The average shrinkage is 2.3%, which Ceramide glucosyltransferase means that the out-of-plane lattice shrinks by about 2.3% along the c-axis. The in-plane epitaxial relationship between the films and the substrate was ATM inhibitor cancer measured by azimuthal scans in skew geometry. Figure 3b shows an XRD 211 pole figure of the as-grown sample measured by setting 2θ = 57.92°. The reflections from EuTiO3 and SrTiO3 overlap in every streak measured by an azimuthal and sample-tilting angular scans. The in-plane fourfold symmetry of the EuTiO3/SrTiO3 orientation relationship is revealed by the four streaks in the pole figure,

which shows an in-plane orientation relationship of EuTiO3〈100〉∥SrTiO 3〈100〉. Evidently, the pole figure provides the same qualitative information as the SAED patterns, in that it reveals a fourfold symmetry and an excellent in-plane alignment of the EuTiO3 films and SrTiO3 substrate. Postannealing of the as-grown sample was carried out in an Ar ambient for 10 h at 1,000°C in order to compare the result with the report where the epitaxial EuTiO3 films were prepared by pulsed laser deposition [11]. Upon postannealing, symmetric HRXRD longitudinal ω- 2θ scans display that the EuTiO3 peaks shift toward lower angles and are superimposed on the SrTiO3 peaks without yielding any impurity phases, as shown in Figure 3a.

The A mode especially is subject to change for high Se concentrations. This fact makes this mode a sensitive Mocetinostat in vitro indicator of variations

in the concentration x. The high-frequency E mode is broadened as in the original data of Richter and Becker [cf. their Figure five(a)]. The this website position of the A and the higher E mode was weighted stronger than the position of the relatively constant A mode and the lower E mode. The value of x was determined to be 0.7, corresponding to BST. Figure 3 Raman spectrum of a single nanowire and representation of the Raman data for Bi 2 (Te 1−x Se x ) 3 . (a) Raman spectrum of a nanowire grown at 480°C. Four peaks at 66, 112, 129, and 164 cm −1 are obtained from fitting Lorentzians. The peaks can be assigned to the Raman modes of Bi2Se2Te. (b) Representation of the Raman data for Bi2(Te 1−x Se x )3 for 0

maximum). The diameter (measured height) of the nanowires is 22.0 nm, corresponding to 23 quintuple layers (QLs) with 1 QL = 0.96 nm. We can conclude that these nanowires were grown along the [110] direction. Figure 4 AFM micrographs of Bi 2 Se 2 Te nanowires on Si. Two nanowires are visible which stick together side by side, having a diameter (height) of 22.0 nm or 23 quintuple see more layers (QLs). The VLS growth mechanism requires the formation of a catalyst-precursor alloy and the subsequent Vorinostat concentration crystallisation out of the supersaturated solution [22]. A metal alloy particle is typically either found at the tip or the root of the nanowire [23]. The samples show root-catalysed growth as can be seen in Figure

1c. A catalyst particle is found at the base of all of the nanowires investigated at this temperature. Tip-based Bi2Se3 nanowire growth was observed by Kong et al. using 20-nm-diameter Au particles in an identical experiment [24]. In contrast, Alegria et al. reported root-based growth of Bi2Se3 nanostructures from an annealed, 5-nm-thick Au layer using metal-organic chemical vapour deposition [18]. The differing growth mechanism was explained by the use of a gas source instead of a solid precursor. Our study suggests that it is not the growth technique that determines the VLS growth mechanism, but rather the size of the catalytic particle. Above a critical size, the catalytic particle is lifted up by the growing nanowire as observed by Kong et al. This effect can be explained by a catalyst-substrate interaction that depends on the size of the catalyst particle. If the Au catalyst alloys with the SiO2/Si substrate, e.g.

Inset: the photograph and schematic structure of the device. To further investigate the JNK inhibitor conduction mechanism in the flexible RRAM, the I-V curves of the ON and OFF states were re-plotted in a dual logarithmic plot. As shown in Figure 3a, the logarithmic plot and linear fitting of the previous I-V curve for the device in LRS show a typical ohmic conduction with a slope of 0.95, which is considered to be the formation of conductive filaments in the memory cell during the set process. On the other hand, the conduction mechanism of the device in

HRS seems to be more complicated, with considerable disparities in negative and positive sweepings. OSI-906 mouse The fitting result for the device in HRS under negative bias is presented in Figure 3b, and the slopes of the curve differ from each other under different voltages. When the electric field is small, the I-V slope is about 1.08, which

conforms to ohmic conduction. However, when the voltage enters into the high electric field, the relationship between logarithm voltage and logarithm current turns to be an aV2 + bV relation, which is the classical space charge-limited conduction (SCLC). However, for the conduction behavior of the OFF state in devices under positive bias (Figure 3c), the slope is estimated to be 1.27 when the electric field is small, and the slope raises to 3.77 when the selleck chemicals electric field is large enough until it approaches the compliance current (1 mA). As it is widely accepted that in oxide-based films the electron hops across the film through the body oxygen vacancies or defects, we attribute the conduction mechanism for the device in HRS under positive bias to be the trap-assisted tunneling (TAT) conduction [29]. When a negative bias was applied on the device, electrons are injected from the top electrode (TE) to the

oxide and then proceed to the bottom electrode (BE). The resistance of TE to oxide is much larger than that of oxide to BE. As a result, the current is limited by the available see more electron in the oxide and leads to SCLC conduction. On the other hand, when a positive voltage was applied on the device, electrons are injected from BE to the oxide and then proceed to the TE. The current is limited by the traps available in the oxide near TE. As a result, the conduction mechanism will possibly be TAT. Figure 3 Dual logarithmic plots of the current–voltage characteristics. (a) ON state device, (b) OFF state device under negative bias, and (c) OFF state device under positive bias. Figure 4 shows the data retention characteristics of the flexible RRAM device at room temperature and under high temperature up to 85°C. Both HRS and LRS were read at 0.1 V for 104 s, and a predetermination of the long-term retention was made. At room temperature, no significant degradation of the memory window was observed, with the HRS ascending slightly.

Nature 1993, 362: 755–758.CrossRefPubMed PR-171 mouse 25. Chen TT, Tao MH, Levy R: Idiotype-cytokine fusion proteins as cancer vaccines. Relative efficacy

of IL-2, IL-4, and granulocyte-macrophage colony-stimulating factor. J Immunol 1994, 153: 4775–4787.PubMed 26. Chu RS, Targoni OS, Krieg AM, Lehmann PV, Harding CV: CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. J Exp Med 1997, 186: 1623–1631.CrossRefPubMed 27. Roman M, Martin-Orozco E, Goodman JS, Nguyen MD, Sato Y, Ronaghy A, Kornbluth RS, Richman DD, Carson DA, Raz E: Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat Med 1997, 3: 849–854.CrossRefPubMed 28. Massa S, Franconi R, Brandi R, Muller A, Mett V, Yusibov V, Venuti A: Anti-cancer activity of plant-produced HPV16 E7 vaccine. Vaccine 2007, 25: 3018–3021.CrossRefPubMed

29. Venuti A, Massa S, Mett V, Dalla Vedova L, Paolini F, Franconi V, Yusibov V: An E7-based therapeutic vaccine protects mice against HPV16 associated cancer. Vaccine 2009, in press. 30. Theobald M, Biggs J, Dittmer D, Levine AJ, Sherman LA: Targeting p53 as a general tumour antigen. Proc Natl Acad Sci USA 1995, 92: 11993–11997.CrossRefPubMed 31. DeLeo AB: p53-based immunotherapy of cancer. Crit Rev Immunol 1998, 18: 29–35.PubMed 32. Chikamatsu K, Nakano K, Storkus WJ, Appella E, Lotze MT, Whiteside TL, DeLeo AB: SB431542 purchase Generation of anti-p53 SB202190 clinical trial cytotoxic T lymphocytes from human peripheral blood using autologous dendritic cells. Clin Cancer Res 1999, 5: 1281–1288.PubMed 33. Gurunathan

S, Klinman DM, Seder RA: DNA vaccines: immunology, application, and optimization. Annu Rev Immunol 2000, 18: 927–974.CrossRefPubMed 34. Guermonprez P, Valladeau J, Zitvogel L, Thery C, Amigorena S: Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 2002, 20: 621–667.CrossRefPubMed 35. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, dipyridamole Akira S: A Toll-like receptor recognizes bacterial DNA. Nature 2000, 408: 740–745.CrossRefPubMed 36. Moniz M, Ling M, Hung CF, Wu TC: HPV DNA vaccines. Front Biosci 2003, 8: 55–68. Review.CrossRef 37. Massa S, Simeone P, Muller A, Benvenuto E, Venuti A, Franconi R: Antitumour activity of DNA vaccines based on the human papillomavirus-16 E7 protein genetically fused to a plant virus coat protein. Hum Gene Ther 2008, 19: 354–64.CrossRefPubMed 38. O’Malley BW Jr, Li D, McQuone SJ, Ralston R: ombination nonviral interleukin-2 gene immunotherapy for head and neck cancer: from bench top to bedside. Laryngoscope 2005, 115: C391–404.CrossRef 39. Ling M, Wu TC: Therapeutic human papillomavirus vaccines. In Cervical cancer: from etiology to prevention. Edited by: Rohan TE, Shah KV. Boston: Kluwer Academic Publishers; 2004:345–376.CrossRef 40.

“
“Background Group III-V semiconductors containing small amounts of bismuth (Bi), popularly known as ‘dilute bismide,’ attracted check details great attention in the past decade. Bismuth

is the largest and the heaviest group V element with its isoelectronic energy level that resides in the valence band of most III-V materials. Incorporation of a small amount of Bi atoms in a common III-V compound is expected to lead to a large bandgap reduction [1] and strong spin-orbit splitting [2]. This provides a new degree of freedom to engineering the band structure for potential optoelectronic and electronic device applications. Under such conditions, it is expected that troublesome hot-hole-induced Auger recombination and inter-valence band absorption (IVBA) processes can be suppressed leading to high efficiency and temperature insensitive lasers for optical communications [3]. Most published literatures so far focus on growth and material properties of GaAsBi with improving quality, making GaAsBi closer to device applications. GaAsBi light-emitting diodes (LEDs) [4] and optically pumped [5] and electrically injected [6] laser diodes have been demonstrated recently. Group III-V semiconductor phosphides are important

materials for optoelectronic devices working at visible and near-infrared wavelength range [7, 8]. The incorporation of Bi into InP can further extend transition wavelengths for optoelectronic devices with aforementioned improved device performances as a result of the suppressed nearly Auger recombination and IVBA processes. Berding et al. theoretically compared InPBi, InAsBi, InSbBi, and HgCdTe, and pointed out that InPBi was much more robust BIBF 1120 in vitro than the others, thus making it as a promising candidate for infrared applications. However, their calculations also showed that InPBi was very difficult to synthesize due to a larger miscibility gap than that of InAsBi and InSbBi [9]. So far, a few works on the optical studies of InP/Bi where the incorporated Bi is only in the doping level [10, 11] were reported. The spectroscopy reveals rich sharp transitions at energy levels close to the InP bandgap at low temperatures. In this work, we investigate the structural and optical properties

of InPBi with Bi composition in the range of 0.6% to 2.4%. The Bi-induced bandgap reduction of around 56 meV/Bi% is obtained. Strong and broad photoluminescence (PL) signals have been observed at transition energy much smaller than the InPBi bandgap. Methods The samples were grown on (100) semi-insulating InP substrates by V90 gas source molecular beam epitaxy (GSMBE). Elemental In and Bi and P2 cracked from phosphine were applied. After the surface oxide desorption of InP substrate at 524°C, a 75-nm undoped InP buffer was grown at 474°C, the VX-680 order normal growth temperature of InP. Then the growth temperature was decreased significantly for InPBi growth. Both the Bi/P ratio and the growth temperature were adjusted to achieve InPBi with various Bi compositions.

All of the slaughter slabs and retail pork meat shops in Chitwan were visited and butchers were interviewed. Sample collection There are 5 slaughter slabs and

5 retail pork meat shops in Chitwan district. Altogether 139 pooled samples of pork meat (each sample contain meat from neck, ham, shoulder check details and skin) were collected aseptically from all of these slaughter slabs and retail pork shops in UV sterilized plastic zipped bags and transported immediately to Veterinary Microbiology Laboratory of the IAAS, Rampur in ice cooled box for further processing. Bacterial culture Isolation and identification of thermophilic Campylobacter spp. was done according to OIE Terrestrial Manual 2008, chapter 2.8.10. The collected samples were immediately processed without storage. About 10 gm of each samples were mixed with 90 ml 0.1% buffered

peptone water (pH 7.2) (M614, HiMedia lab, Mumbai, India) and homogenized manually GDC 0032 for pre-enrichment. One volume of homogenized fluid was added to nine volume of Bolton broth (CM0983, Oxoid ltd, Basingstoke, Hampshire, England) for enrichment and then subjected to incubation in microaerophilic atmosphere obtained by burning candle in candle jar (BD1777SE, Don Whitely Scientific Ltd, England) at 37°C for 5 hours and then at 42°C for next 43 hours. Following incubation, one buy Pevonedistat loopful of broth culture was streaked on modified CCDA (mCCDA) and incubated at 42°C in a microaerophilic atmosphere for 48 hrs in candle jar. When suspected colonies were detected, confirmatory tests including Gram,s stain, growth at 25°C, oxidase and catalase tests, sensitivity to nalidixic acid and cephalothin and hippurate hydrolysis were performed. Antibiogram of the isolated species Antibiogram of identified Campylobacter Y-27632 2HCl spp. was evaluated against nine different antibiotics (ampicillin, chloramphenicol, ciprofloxacin, nalidixic acid, erythromycin, tetracycline, gentamicin, colistin, and cotrimoxazole) by disc diffusion method following CLSI guidelines.

Platinum loop was used to pick pure Campylobacter spp. colonies from the mCCDA plates and turbid suspension was made by emulsifying colonial growth in BHI broth. The turbidity of the inoculums was adjusted to the equivalent turbidity of 0.5 McFarland standards and the broth was incubated in microphilic condition for 48 hours in anaerobic jar with lighting candle. After incubation, 100 μl of Brain Heart Infusion broth (M210, HiMedia lab, Mumbai, India) was dispersed over the surface of a Mueller Hinton Agar (MHA) (M173, HiMedia lab, Mumbai, India) with 5% defibrinated sheep blood to produce a lawn of confluent of bacteria on the surface of agar. Using sterile tweezers, antimicrobial discs were placed widely spaced aseptically on the surface of MHA plate. Tweezers were reflamed after application of each disc. The plates were then incubated in microaerophilic condition at 37°C for 24 hours.

All people age chronologically at the same speed, but the way in which people

physically age depends on their genetics, health habits, illnesses, environment and their occupation (Naumanen 2006). In general, functional capacities, mainly physical, show a AP26113 clinical trial declining trend after the age of 30, and the trend can become critical after the next 15–20 years if the physical demands of work do not decline (Ilmarinen 2001). These declines are primarily associated with reductions in cardiovascular, respiratory, metabolic and muscular functions. Declining functional capacities may affect individuals’ ability to perform the tasks that their jobs demand. Workers may find themselves working closer to their BMN 673 datasheet maximal capacities, putting themselves at greater risk for chronic fatigue or musculoskeletal injuries (Kenny et al. 2008). Apart from changes in physical capacities of the ageing worker, also changes in mental functioning are reported in the literature. The most important changes in mental functions are related to the weakening of precision and the speed of perception (Ilmarinen 2001). On the other hand, some mental characteristics can also strengthen with age, such

as the ability to deliberate and reason (Baltes and Smith 1990; Schaie 1994). Although the group of ageing workers has attracted substantial research interest, so far their health and well-being have not been studied extensively; and therefore, the actual health implications of longer working careers remain unclear. The concept of need for recovery from work could be considered an important perspective to study health effects C646 in vitro of working at an older age. Need for recovery represents short-term effects of a day of work (Sluiter et al. 2001) and was defined as the need to recuperate from work-induced fatigue, primarily experienced after a day of work (Jansen

et al. 2002). Need for recovery can be observed especially during the last hours of work and immediately after work. It is characterized by temporary feelings of overload, irritability, social withdrawal, lack of energy for new effort and reduced performance (Van Veldhoven 2008). Need for recovery from work can be recognized in the off-work situation by feelings of ‘wanting to be left alone for a while’ or ‘having to lie-down for a while’ (Sluiter et al. Rutecarpine 2001). Repeated insufficient recovery from work-induced fatigue is seen as the start of a vicious circle where extra effort has to be exerted at the beginning of every new working period to rebalance the suboptimal psycho-physiological state and to prevent performance breakdown (Sluiter et al. 1999). Repeated insufficient recovery from work is related to health problems (Meijman 1989; Van der Beek et al. 1995). A study among truck drivers has shown that high need for recovery was prospectively related to increased sickness absence (de Croon et al. 2003).

By imaging using the near infra red cell tracking combined to bioluminescence we showed the active migration and localisation of the endothelial precursor cells in the sites where the tumor cells metastasize. This was confirmed by applying several methods including MRI (Magnetic Resonance Imaging), near-infrared fluorescence imaging and flow cytometry to detect and quantify the efficacy of the EPC seeking into tumor sites. [1] Folkman J, N Engl J Med., 285:1182–1186 (1971)

[2] Peters BA et al. Nat Med., 11(3):261–2 (2005) [3] Gao D, Nolan DJ, Mellick AS, et al. Science. 319(5860), 195, (2008) Poster No. 194 Immunotherapeutic Strategy against EBV Latency 4EGI-1 in vivo II Malignancies Olivier SRT2104 price Morales 1 , Stéphane Depil1,2, Céline Miroux1, Violaine Francois1, Françoise Dufosse3, Claude Auriault4, Yvan De Launoit1, Véronique Pancre1, Nadira Delhem1 1 CNRS, UMR 8161, Institut de Biologie de Lille, Lille, France, 2 Service des Maladies du sang, CHRU, Lille, France, 3 Laboratoire d’Immunologie-HLA-Transplantation, CHRU, Lille, France, 4 CNRS, UMR 6097, IPMC, Nice, France The Epstein-Barr virus (EBV) is associated with several malignant diseases which can be distinguished by their patterns of viral latent gene expression. The latency II (lat.II) program is limited to the expression of the non-immunodominant antigens EBNA-1, LMP-1 and LMP-2, and is particularly

associated with Hodgkin’s disease, nasopharyngeal carcinomas and peripheral T/NK-cell lymphomas. Knowing that CD4+ T lymphocytes may play a crucial role in controlling these EBV malignancies, Methane monooxygenase we favoured an immunotherapeutic approach, based on the stimulation of a specific CD4+ T cell response. We used the TEPITOPE software to predict promiscuous MHC class II epitopes derived from the latency II antigens EBNA-1, LMP-1 and LMP-2. The predicted peptides were then AZD2171 price submitted to peptide-binding assay on HLA II purified molecules,

which allowed the selection of 6 peptides (EBNA-1: 3, LMP-1: 1, LMP-2: 2) with a highly promiscuous capability of binding. The peptide cocktail was highly immunogenic in Aβ°-DR1 transgenic mice, leading to a specific cellular and humoral Th1 response. Every peptides used in the cocktail or individually were also recognized by human CD4+ memory T cells from healthy donors expressing various HLA II genotypes and from patients with Hodgkin’s lymphoma (HL). We have then generated peptide-specific CD4+ cell lines, and assessed their cytotoxic potential to lyse lymphoblastoid cell lines (LCLs, Lat.III), or other EBV expressing cell lines such as T cell line (NC5, Lat.II) and monocyte cell lines (TE1, Lat.II). Finally, any changes in CD4+CD25+ regulatory T cell activity were observed in response to the peptide cocktail; avoiding the risk of aggravation of the pre-existing immuno-suppressive microenvironment, already known in EBV+ associated malignancies.