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In recent years, the use of immune checkpoint inhibitors (ICIs) in combination withapproved or experimental vaccines has proven to be a promising approach to improve vaccineimmunogenicity and efficacy. This strategy seeks to overcome the immunosuppressive mechanismsassociated with the vaccine response, thereby achieving increased immunogenicity and efficacy. Most of the information on the use of ICIs combined with vaccines derives from studies on certain antitumor vaccines combined with monoclonal antibodies (mAbs) against either cytotoxic T lymphocyteassociatedprotein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand1 (PD-L1). However, over the past few years, emerging strategies to use new-generation ICIs asmolecular adjuvants are paving the way for future advances in vaccine research. Here, we review thecurrent state and future directions of the use of ICIs in experimental and clinical settings, includingmAbs and alternative new approaches using antisense oligonucleotides (ASOs), small non-codingRNAs, aptamers, peptides, and other small molecules for improving vaccine efficacy. The scopeof this review mainly includes the use of ICIs in therapeutic antitumor vaccines, although recentresearch on anti-infective vaccines will also be addressed.

A better understanding of the complex interactions between the immune system and tumour cells from different origins has opened the possibility to design novel procedures of antitumoral immunotherapy. One of these novel approaches is based on the use of autologous or allogeneic natural killer (NK) cells to treat cancer. In the last decade, different strategies to activate NK cells and their use in adoptive NK cell-based therapy have been established. Although NK cells are often considered as a uniform cell population, several phenotypic and functionally distinct NK cells subsets exist in healthy individuals, that are differentially affected by ageing or by apparently innocuous viruses such as cytomegalovirus (CMV). In addition, further alterations in the expression of activating and inhibitory receptors are found in NK cells from cancer patients, likely because of their interaction with tumour cells. Thus, NK cells represent a promising strategy for adoptive immunotherapy of cancer already tested in phase 1/2 clinical trials. However, the existence of NK cell subpopulations expressing different patterns of activating and inhibitory receptors and different functional capacities, that can be found to be altered not only in cancer patients but also in healthy individuals stratified by age or CMV infection, makes necessary a personalized definition of the procedures used in the selection, expansion, and activation of the relevant NK cell subsets to be successfully used in NK cell-based immunotherapy.

CD56+ T cells are generally recognized as a distinct population of T cells and are categorized as NKT-like cells. Although our understanding of NKT-like cells is far from satisfactory, it has been shown that aging and a number of disease situations have impacted these cells. To construct an overview of what is currently known, we reviewed the literature on human NKT-like cells. NKT-like cells are highly differentiated T cells with “CD1d-independent” antigen recognition and MHC-unrestricted cell killing. The genesis of NKT-like cells is unclear; however, it is proposed that the acquisition of innate characteristics by T cells could represent a remodeling process leading to successful aging. Additionally, it has been shown that NKT-like cells may play a significant role in several pathological conditions, making it necessary to comprehend whether these cells might function as prognostic markers. The quantification and characterization of these cells might serve as a cutting-edge indicator of individual immune health. Additionally, exploring the mechanisms that can control their killing activity in different contexts may therefore result in innovative therapeutic alternatives in a wide range of disease settings.

Aortic stenosis (AS) is a frequent cardiac disease in old individuals, characterized by valvular calcification, fibrosis, and inflammation. Recent studies suggest that AS is an active inflammatory atherosclerotic-like process. Particularly, it has been suggested that several immune cell types, present in the valve infiltrate, contribute to its degeneration and to the progression toward stenosis. Furthermore, the infiltrating T cell subpopulations mainly consist of oligoclonal expansions, probably specific for persistent antigens. Thus, the characterization of the cells implicated in the aortic valve calcification and the analysis of the antigens to which those cells respond to is of utmost importance to develop new therapies alternative to the replacement of the valve itself. However, calcified aortic valves have been only studied so far by histological and immunohistochemical methods, unable to render an in-depth phenotypical and functional cell profiling. Here we present, for the first time, a simple and efficient cytometry-based protocol that allows the identification and quantification of infiltrating inflammatory leukocytes in aortic valve explants. Our cytometry protocol saves time and facilitates the simultaneous analysis of numerous surface and intracellular cell markers and may well be also applied to the study of other cardiac diseases with an inflammatory component.

Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. We have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Here, we expand our results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, we studied the polyfunctional responses (degranulation, IFN-γ and TNF-α production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4-CD8- (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). Our results show that CD57 expression by T-cells is not only a hallmark of CMV infection in young individuals but also at older ages. CD57+ T-cells are more polyfunctional than CD57− T-cells regardless of age. CMV-seronegative individuals have no or a very low percentages of cytotoxic CD4+ T-cells (CD1017a+) and CD4+CD57+ T-cells, supporting the notion that the expansion of these T-cells only occurs in the context of CMV infection. There was a functional shift in T-cells associated with CMV seropositivity, except in the NKT-like subset. Here, we show that the effect of CMV infection and age differ among T-cell subsets and that CMV is the major driving force for the expansion of highly polyfunctional CD57+ T-cells, emphasizing the necessity of considering CMV serology in any study of immunosenescence.

Immunosenescence affects innate and adaptive immunity impairing the response to pathogens and vaccines. Chronic infection with cytomegalovirus (CMV) has been shown to drive “early immunosenescence” and can considerably affect both the function and phenotype of immune cells, especially T cells. We have previously shown that the expression of CD57, CD300a, and CD161 was differentially affected by age and chronic CMV infection, indicating that these markers are a hallmark of CMV infection and T-cell aging. The aim of this present study was to clarify whether these 3 markers define distinct T-cell subpopulations with a specific functional and molecular signature. Specifically, we analyzed the effect of age and chronic CMV infection on the functionality of T cells according to CD161, CD300a, and CD57 expression. We found that these markers defined different T-cell subsets, both at the phenotypic and functional levels. CD57 was the best biomarker for CD4+ T-cell cytotoxicity and was a hallmark of CMV infection. CD300a+ T cells were heterogeneous and included different cell subsets. The population of CD161+ T cells dramatically decreased with age, independently of CMV infection, and represented a sign of age-associated immune system alterations. The latter could contribute to an increased risk of autoimmune disease and infection in older adults. Our results underline the importance of better understanding the factors involved in the immunosenescence process to be able to uncover new biomarkers and open new avenues for the investigation and development of novel age-related disease therapies.

Background: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. Methods: We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. Results: NK cells, CD56&minus, T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56&minus, T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1&minus, TIGIT+TACTILE+ NK cells and DNAM-1&minus, TIGIT+TACTILE+ CD56&minus, T cells were associated with a better survival of AML patients. Conclusions: The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade.

Alzheimer’s disease (AD) represents the most common cause of dementia in the elderly. AD is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although the aetiology of AD is not clear, both environmental factors and heritable predisposition may contribute to disease occurrence. In addition, inflammation and immune system alterations have been linked to AD. The prevailing hypothesis as cause of AD is the deposition in the brain of amyloid beta peptides (Aβ). Although Aβ have a role in defending the brain against infections, their accumulation promotes an inflammatory response mediated by microglia and astrocytes. The production of proinflammatory cytokines and other inflammatory mediators such as prostaglandins and complement factors favours the recruitment of peripheral immune cells further promoting neuroinflammation. Age-related inflammation and chronic infection with herpes virus such as cytomegalovirus may also contribute to inflammation in AD patients. Natural killer (NK) cells are innate lymphoid cells involved in host defence against viral infections and tumours. Once activated NK cells secrete cytokines such as IFN-γ and TNF-α and chemokines and exert cytotoxic activity against target cells. In the elderly, changes in NK cell compartment have been described which may contribute to the lower capacity of elderly individuals to respond to pathogens and tumours. Recently, the role of NK cells in the immunopathogenesis of AD is discussed. Although in AD patients the frequency of NK cells is not affected, a high NK cell response to cytokines has been described together with NK cell dysregulation of signalling pathways which is in part involved in this altered behaviour.

Resumen Antecedentes y objetivo La determinacion de inmunoglobulinas en suero y, concretamente de IgG y de subclases de IgG, es fundamental para el diagnostico clinico de numerosas patologias. Los metodos de deteccion habituales proporcionan resultados diferentes segun el analizador utilizado. El objetivo de este estudio fue comparar los resultados obtenidos mediante dos analizadores diferentes para la concentracion de IgG y de subclases de IgG. Materiales y metodos Se analizaron un total de 116 muestras de suero, independientemente del diagnostico clinico de los pacientes a los que pertenecian dichas muestras. Los analisis se realizaron sobre las plataformas BNII® System (Siemens Healthcare GmbH, Alemania) y Optilite® (The Binding Site Group Ltd., Birmingham). Resultados La correlacion entre la concentracion de IgG total (mg/dl) y el sumatorio de las concentraciones de subclases de IgG detectadas de manera individual fue mayor usando el analizador Optilite® (0,976 vs. 0,866). El porcentaje de concordancia vario del 43% hasta 71%, siendo el limite inferior para la concordancia de IgG3. Se detecto una ausencia de la proporcion fisiologica normal de subclases de IgG (IgG1 >IgG2 >IgG3 >IgG4) al utilizar BNII®. Dichos resultados fueron consecuencia de que la concentracion de IgG3 por BNII® fue significativamente inferior a la obtenida por Optilite® (p Conclusiones Las diferencias existentes entre los resultados obtenidos por ambos metodos analiticos utilizados sugieren que dichos ensayos no deben ser intercambiables, sino que cada laboratorio debe utilizar un unico analizador y estandarizar los rangos de referencia segun sus resultados.

Cytomegalovirus (CMV), a member of the β-herpesvirus family, is a major complicating infection in transplant patients. CMV latency has a long-term impact on CD8+ T-cell differentiation. It is unclear, however, whether this effect can be detected in one-year period. To investigate this, we analyzed the remodeling of the CD8+ T-cell compartment during the first year after solid organ transplantation. A total of 55 kidney or lung transplant patients were recruited. CD8+ T-cell subsets were prospectively analyzed at pretransplant, at 3 or 6months and 12months after transplantation (mo post-Tx). A significant increase in the frequency of CD27-CD28-CD8+ T cells (from 32.8% to 42.3%; p=0.014) was observed from pretransplant to 12mo post-Tx. Further analysis, however, showed that the largest expansion was observed from 3/6 to 12mo post-Tx whereas small non-significant variations were observed from pretransplant to 3/6mo post-Tx. The adjusted analysis showed that age and CMV seropositivity were statistically associated with the baseline frequency of CD27-CD28-CD8+ T cells. Additionally, CMV replication was related to the posttransplant expansion of this subpopulation, since it was not observed in patients without CMV viremia (24% vs. 4.2%). The results indicate that the expanded frequency associated with late CMV replication is additive to the baseline frequency related to aging and CMV seropositivity. If the expanded frequency remains at this high level for a long period it might have clinical consequences related to the control of future reactivations of CMV or of other related viruses.

Since the discovery of lymphocytes with immunosuppressive activity, increasing interest has arisen in their possible influence on the immune response induced by vaccines. Regulatory T cells (Tregs) are essential for maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory diseases. However, they also limit beneficial immune responses by suppressing anti-infectious and anti-tumor immunity. Mounting evidence suggests that Tregs are involved, at least in part, in the low effectiveness of immunization against various diseases where it has been difficult to obtain protective vaccines. Interestingly, increased activity of Tregs is associated with aging, suggesting a key role for these cells in the lower vaccine effectiveness observed in older people. In this review, we analyze the impact of Tregs on vaccination, with a focus on older adults. Finally, we address an overview of current strategies for Tregs modulation with potential application to improve the effectiveness of future vaccines targeting older populations.

Natural killer (NK) cells are lymphocytes of the innate immune response characterized by their role in the destruction of tumor cells. Activation of NK cells depend on a fine balance between activating and inhibitory signals mediated by different receptors. In recent years, a family of paired receptors that interact with ligands of the Nectin/Nectin-like (Necl) family has attracted great interest. Two of these ligands, Necl-5 (usually termed CD155 or PVR) and Nectin-2 (CD112), frequently expressed on different types of tumor cells, are recognized by a group of receptors expressed on T and NK cells that exert opposite functions after interacting with their ligands. These receptors include DNAM-1 (CD226), TIGIT, TACTILE (CD96) and the recently described PVRIG. Whereas activation through DNAM-1 after recognition of CD155 or CD112 enhances NK cell-mediated cytotoxicity against a wide range of tumor cells, TIGIT recognition of these ligands exerts an inhibitory effect on NK cells by diminishing IFN-γ production, as well as NK cell-mediated cytotoxicity. PVRIG has also been identified as an inhibitory receptor that recognizes CD112 but not CD155. However, little is known about the role of TACTILE as modulator of immune responses in humans. TACTILE control of tumor growth and metastases has been reported in murine models, and it has been suggested that it negatively regulates the anti-tumor functions mediated by DNAM-1. In NK cells from patients with solid cancer and leukemia, it has been observed a decreased expression of DNAM-1 that may shift the balance in favor to the inhibitory receptors TIGIT or PVRIG, further contributing to the diminished NK cell-mediated cytotoxic capacity observed in these patients. Analysis of DNAM-1, TIGIT, TACTILE and PVRIG on human NK cells from solid cancer or leukemia patients will clarify the role of these receptors in cancer surveillance. Overall, it can be speculated that in cancer patients the TIGIT/PVRIG pathways are upregulated and represent novel targets for checkpoint blockade immunotherapy.

The incidence of some types of tumours has increased progressively in recent years and is expected to continue growing in the coming years due in part to the aging of the population. The design of new therapies based on natural killer (NK) cells opens new possibilities especially for the treatment of elderly patients who are particularly susceptible to the toxicity of conventional chemotherapy treatments. In recent years, the potential use of NK cells in cancer immunotherapy has been of great interest thanks to advances in the study of NK cell biology. The identification of key points (checkpoints) in the activation of NK cells that can be regulated by monoclonal antibodies has allowed the design of new therapeutic strategies based on NK cells. However, there are still limitations for its use and the first clinical trials blocking KIR inhibitory receptors have shown little efficacy by inhibiting the maturation of NK cells. Blockade of other inhibitory receptors such as TIGIT, TIM3, LAG3 and PD1 may represent novel strategies to increase NK function in cancer patients. Altogether, the identification of NK cell and tumour cell markers of resistance or susceptibility to the action of NK cells will contribute to identifying those patients that will most likely benefit from NK cell-based immunotherapy.

This cross-sectional study analyzes factors associatedwith the development of CMV-specific CD8þ response,measured by IFNg production after cytomegalovirus(CMV) peptide stimulation, in CMV-seropositive solidorgan transplantation candidates. A total of 114candidates were enrolled, of whom 22.8% (26/114)were nonreactive (IFNg

En la actualidad los docentes universitarios tienen el reto de enseñar a la conocida como “generación Y”, alumnos nacidos entre los años 1980 y 2000, los cuales no han conocido el mundo sin internet o teléfono móvil. Esto por supuesto implica que el acercamiento al conocimiento, y por tanto los modos de aprendizaje, son completamente diferentes a los de generaciones anteriores. Esto unido a la implementación de las nuevas titulaciones acordes con el proceso de convergencia europea y el sistema de créditos ECTS, y siguiendo los desafíos de la enseñanza contemplados en el Espacio Europeo de Educación Superior (EEES), hace inevitable la implementación de nuevas formas de comunicación entre los alumnos y los profesores en el ámbito Universitario. Aunque en este aspecto la mayoría de las Universidades cuentan ya con diferentes herramientas de e-Learning, su uso e implementación en algunas ocasiones puede resultar insuficiente. En este escenario, por el contrario, son muchas las posibilidades que ofrecen las redes sociales y su extenso uso entre el alumnado, quien accede generalmente con mucha frecuencia a sus perfiles y grupos, proporcionando una comunicación rápida, fácil y flexible. En el presente proyecto de innovación docente hemos combinado el uso de un grupo de Facebook con los recursos tradicionales en la docencia relativa a la asignatura de Inmunología, usando esta red social como herramienta de apoyo para compartir materiales e información. Todo ello buscando un nuevo ambiente de comunicación más directo entre alumnos y profesorado, sin por supuesto tener que sustituir las vías de comunicación formales como el correo electrónico y Moodle. Esto nos ha permitido evaluar su uso, participación y satisfacción entre el alumnado que ha participado en el proyecto. Nowadays, University teachers face the challenge of teaching the so-called “Y generation”, students born between 1980 and 2000, who haven't experienced their lives without the Internet or the mobile phone. This has a direct consequence on their approach to knowledge and, therefore, to the learning styles, which are completely different to those of former generations. This fact, together with the implementation of new degrees more in line with the European convergence process and the ECTS credit system, and following the educative challenges included in the new European Space of Higher Education (EEES), makes it necessary to implement new forms of communication between pupils and teachers in the university context. Although most universities already make use of different e-Learning tools, their use and implementation can sometimes be insufficient. In this scenery, on the contrary, the social networking sites and their extended use by students, who check their profiles and groups very often, offer a lot of possibilities, as they allow a fast, easy and flexible communication. In the present project of teaching innovation, we have combined the use of a Facebook group with the traditional resources used in Immunology, so that this social networking site becomes a support tool to share materials and information. In the same sense, we look for a new atmosphere where a more direct communication between students and teachers is possible, without avoiding the more formal forms of communication such as the email or Moodle. This has allowed us to evaluate its use, participation and satisfaction, both between the students and the teachers taking part in the project.

Ankylosing spondylitis (AS) is very often associated with human leukocyte antigen (HLA), particularly HLA-B*27. However, the strength of this association and clinical features may vary in different ethnic groups. Our study aims to assess the distribution of HLA-A, -B, -Cw and DRB1 alleles in Moroccan patients with AS and to compare the clinical features of AS and the frequencies of HLA-B27 in patients from Morocco with other series. Seventy-five patients diagnosed with AS and assessed for clinical manifestations were selected and compared to 100 healthy controls. HLA class I and II antigens were typed by polymerase chain reaction sequence-specific oligonucleotide. HLA-B27 subtypes were studied by polymerase chain reaction amplification with sequence-specific primers. HLA-B27 was found in 64% of patients. It was positively associated with younger age at disease onset, family history, and uveitis while it had a negative association with late onset. Six B*27 subtypes were identified in the AS group. HLA-B*2705 and B*2702 were the most common observed subtypes. Among other HLA genes, a significant increase in the prevalence of HLA-Cw*02 and HLA-DRB*15 was found in AS patients. HLA-B27 is involved in the predisposition of AS in the Moroccan population. HLA-B*2705 and B*2702 were the predominant subtypes supporting previous reports in Caucasian spondyloarthropathies. Other HLA genes, HLA-Cw*02 and HLA-DRB1*15, seem to confer predisposing effect to the disease. However, the lower frequency of HLA-B27 compared to the literature in our study suggests the existence of different genetic and/or environmental factors in Morocco.

Immunosenescence is a progressive deterioration of the immune system with ageing. It affects both innate and adaptive immunity limiting the response to pathogens and to vaccines. As chronic cytomegalovirus (CMV) infection is probably one of the major driving forces of immunosenescence, and its persistent infection results in functional and phenotypic changes to the T-cell repertoire, the aim of this study was to analyze the effect of CMV-seropositivity and ageing on the expression of CD300a and CD161 inhibitory receptors, along with the expression of CD57 marker on CD4+, CD8+, CD8+CD56+ (NKT-Like) and CD4−CD8− (DN) T-cell subsets. Our results showed that, regardless of the T-cell subset, CD57−CD161−CD300a+ T-cells expand with age in CMV-seropositive individuals, whereas CD57−CD161+CD300a+ T-cells decrease. Similarly, CD57+CD161−CD300a+ T-cells expand with age in CMV-seropositive individuals in all subsets except in DN cells and CD57−CD161+CD300a− T-cells decrease in all T-cell subsets except in CD4+ T-cells. Besides, in young individuals, CMV latent infection associates with the expansion of CD57+CD161−CD300a+ CD4+, CD57−CD161−CD300a+ CD4+, CD57+CD161−CD300a+ CD8+, CD57−CD161−CD300a+ CD8+, CD57+CD161−CD300a+ NKT-like and CD57+CD161−CD300a+ DN T-cells. Moreover, in young individuals, CD161 expression on T-cells is not affected by CMV infection. Changes of CD161 expression were only associated with age in the context of CMV latent infection. Besides, CD300a+CD57+CD161+ and CD300a−CD57+CD161+ phenotypes were not found in any of the T-cell subsets studied except in the DN subpopulation, indicating that in the majority of T-cells CD161 and CD57 do not co-express. Thus, our results show that CMV latent infection impact on the immune system depends on the age of the individual, highlighting the importance of including CMV serology in any study regarding immunosenescence.

NK cells are key players in the innate immune response against virus infection and tumors. Here we describe the current knowledge on age-associated changes in NK cells and the role of persistent CMV infection in configuring NK cell compartment in the elderly. Aging but not CMV causes a redistribution of NK cell subsets as shown by a decrease of CD56bright cells and an increase of CD56-CD16+ NK cells. On the contrary the changes in CD56dimCD16+ NK cells are compatible with the accumulation of CD57+ long-lived NK cells that can also be observed in young CMV-seropositive individuals. NK cell function and dynamics in the elderly will be related not only with age but also with exposure to pathogens, especially CMV.

A predator–prey model was applied to the red grouper Epinephelus morio fishery from Yucatan, Mexico, with the aim of understanding the spatial behaviour of a mid-sized fishing fleet. The heterogeneity of the environment was considered, and different habitat quality levels were determined to address environmental differences. The behaviour of the fleet was also evaluated based on a simulation of restricted fishing areas (RFA). The model was applied utilising 5 years of information on catch and fishing effort (1973–1977). Four levels of habitat quality were defined (low, medium, high and exceptional). The total costs and revenue for a fishing expedition in the areas of exceptional habitat quality were higher due to their location farthest from the base port. The fleet was most efficient during the winter at locations in the eastern continental shelf, with the number of these areas clearly decreasing in the autumn. The model simulation of the RFA showed a total revenue reduction of 7–27 % in scenarios of RFA for adult protection. When the RFA was implemented for the protection of juvenile fish, the total revenue was not reduced, indicating that this type of RFA might be a feasible management strategy for a sustainable fishery.

Background Several evidences support the existence of cytokine deregulation in acute myeloid leukemia (AML) patients that may be associated with pathogenesis, disease progression and patient survival. Methods In the present study, we analyzed plasma levels of pro- and anti-inflammatory cytokines in AML patients and age-matched healthy donors. TNF-α, IL-6, IL-1β, IL-2, IFN-γ, IL-17A, IL-12p70, IL-8, IL-10, IL-4 and IL-5 were analyzed using fluorescent bead-based technology and TGF-β by ELISA technique. Because age-associated differences in cytokine profiles have been described, patients and healthy individuals were divided into two age groups: up to 65 years and over 65 years. Results Our results showed that plasma TNF-α, IL-6 and IL-10 levels were higher in AML patients from both groups of age. IL-8 was increased in AML patients less than 65 years while the plasma concentrations of IL-4, IL-5 and IL-12p70 were significantly higher only in elderly AML patients compared with aged-matched healthy controls. Moreover, plasma levels of IL-6 and IL-10 were associated with patient survival and event-free survival. Conclusions An aberrant production of the pro-inflammatory cytokines IL-6 and TNF-α and the anti-inflammatory cytokine IL-10 is observed in AML patients. Low levels of IL-6 and high levels of IL-10 represent favorable prognostic factors for survival in AML patients. These results support the idea that cytokine deregulation may be useful as a marker for predicting clinical evolution in AML patients.

The differential impact of ageing and cytomegalovirus (CMV) latent infection on human T-cell subsets remains to some extent controversial. The purpose of this study was to analyse the expression of the transcription factors T-bet and Eomes and CD57 on CD4+, CD4(hi)CD8(lo) and CD8+ T-cell subsets in healthy individuals, stratified by age and CMV serostatus. The percentage of CD4+ T-cells expressing T-bet or Eomes was very low, in particular in CD4+ T-cells from young CMV-seronegative individuals, and were higher in CMV-seropositive older individuals, in both CD57 and CD57+ CD4+ T-cells. The study of the minor peripheral blood double-positive CD4(hi)CD8(lo) T-cells showed that the percentage of these T-cells expressing both Eomes and T-bet was higher compared to CD4+ T-cells. The percentage of CD4(hi)CD8(lo) T-cells expressing T-bet was also associated with CMV seropositivity and the coexpression of Eomes, T-bet and CD57 on CD4(hi)CD8l(o) T-cells was only observed in CMV-seropositive donors, supporting the hypothesis that these cells are mature effector memory cells. The percentage of T-cells expressing Eomes and T-bet was higher in CD8+ T-cells than in CD4+ T-cells. The percentages of CD8+ T-cells expressing Eomes and T-bet increased with age in CMV-seronegative and -seropositive individuals and the percentages of CD57 CD8+ and CD57+ CD8+ T-cells coexpressing both transcription factors were similar in the different groups studied. These results support that CMV chronic infection and/or ageing are associated to the expansion of highly differentiated CD4+, CD4(hi)CD8(lo) and CD8+ T-cells that differentially express T-bet and Eomes suggesting that the expression of these transcription factors is essential for the generation and development of an effector-memory and effector T lymphocytes involved in conferring protection against chronic CMV infection.

Cytomegalovirus (CMV), a member of the β-herpesvirus family, is a major complicating infection in transplant patients. CMV latency has a long-term impact on CD8

• BIOEF-EiTB Maratoia Pediatric Cancer. Beca BIO13/CI/011, para Francisco Borrego Rabasco • BIOEF-EiTB Maratoia Transplantation. Beca BIO14/TP/001, para Susana Larrucea Bilbao • Ministerio de Economia y Competitividad. Beca SAF2013-46161-R, para Raquel Tarazona Rabasco • Ministerio de Salud. Beca PI13/02691, para Rafael Solana Lara