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1.
Invest. educ. enferm ; 42(1): 177-192, 20240408. ilus, tab
Article in English | LILACS, BDENF - Nursing, COLNAL | ID: biblio-1554633

ABSTRACT

Objective. This study aimed to the effects of the Health Action Process Approach (HAPA) in promoting the quality of nurses' communication skills among nurses. Methods.The present quasi-experimental research was conducted on 148 nurses (76 in the intervention and 72 in the control group) in Yazd province (Iran). In this study, the total number of nurses in one hospital was selected as the intervention group, while the nurses from another hospital were chosen as the control group. The participants were recruited from public hospitals in Ardakan and Meibod cities. The data collection instrument was a questionnaire based on the Health Action Process Approach (HAPA) Constructs and a communicative skill questionnaire. The data were collected from the two groups before, one month after, and four months after the intervention. The control group did not receive any educational training during the course of the study. Results. In the pretest, no statistically significant difference was found between the intervention and control groups regarding the behavioral stages of effective communication with patients. In the posttest, the mean task self-efficacy score was significantly increased in the intervention group compared to the control (p<0.001). The mean coping self-efficacy score was also significantly higher in the intervention group than the control in the posttest (p<0.001). Moreover, the mean coping planning score was significantly increased in the post-test intervention group(p<0.001). The mean communicative skill score was also significantly increased in the intervention group compared to the post-test control (p=0.03). Conclusion. The intervention used in the present study based on the target model (HAPA) significantly affected nurses' self-efficacy and communicative skills in the experimental group.


Objetivo. Evaluar el efecto del enfoque del proceso de acción sanitaria (Health Action Process Approach (HAPA), en inglés) en la promoción de la calidad de las habilidades de comunicación de las enfermeras. Métodos. La presente investigación cuasiexperimental se llevó a cabo con 148 enfermeras (76 en el grupo de intervención y 72 en el de control) de la provincia de Yazd (Irán). Los participantes fueron reclutados en los hospitales públicos de las ciudades de Ardakan y Meibod. El instrumento de recogida de datos fue un cuestionario basado en los constructos HAPA y un cuestionario de habilidades comunicativas. Se recogieron datos de los dos grupos antes, un mes después y cuatro meses después de la intervención. El grupo de control no recibió ninguna formación educativa durante el estudio. Resultados. En la preprueba, no se encontraron diferencias estadísticamente significativas entre los grupos de intervención y de control en cuanto a las etapas conductuales de la comunicación eficaz con los pacientes. En la prueba posterior, la puntuación media de autoeficacia en la tarea aumentó significativamente en el grupo de intervención en comparación con el grupo de control (p<0.001). La puntuación media de autoeficacia en el afrontamiento también fue significativamente mayor en el grupo de intervención que en el grupo de control en el postest (p<0.001). Además, la puntuación media en planificación del afrontamiento aumentó significativamente en el grupo de intervención después de la prueba (p<0.001). La puntuación media en habilidades comunicativas también aumentó significativamente en el grupo de intervención en comparación con el grupo de control después de la prueba (p=0.03). Conclusión.La intervención utilizada en el presente estudio basada en el modelo HAPA mejoró significativamente la autoeficacia y las habilidades comunicativas de las enfermeras del grupo experimental.


Objetivo. Avaliar o efeito da Abordagem do Processo de Ação em Saúde (HAPA) na promoção da qualidade das habilidades de comunicação dos enfermeiros. Métodos. A presente pesquisa quase-experimental foi realizada com 148 enfermeiros (76 no grupo de intervenção e 72 no grupo de controle) da província de Yazd (Irã). Os participantes foram recrutados em hospitais públicos nas cidades de Ardakan e Meibod. O instrumento de coleta de dados foi um questionário baseado nos construtos do HAPA e um questionário de habilidades de comunicação. Os dados foram coletados dos dois grupos antes, um mês depois e quatro meses após a intervenção. O grupo de controle não recebeu nenhum treinamento educacional durante o estudo. Resultados. No pré-teste, não foram encontradas diferenças estatisticamente significativas entre os grupos de intervenção e controle em termos de estágios comportamentais da comunicação eficaz com os pacientes. No pós-teste, a pontuação média de autoeficácia na tarefa aumentou significativamente no grupo de intervenção em comparação com o grupo de controle (p<0.001). A pontuação média de autoeficácia de enfrentamento também foi significativamente maior no grupo de intervenção do que no grupo de controle no pós-teste (p<0.001). Além disso, a pontuação média do planejamento de enfrentamento aumentou significativamente no grupo de intervenção após o pós-teste (p<0.001). A pontuação média em habilidades de comunicação também aumentou significativamente no grupo de intervenção em comparação com o grupo de controle no pós-teste (p=0.03). Conclusão. A intervenção usada no presente estudo com base no modelo HAPA melhorou significativamente a autoeficácia e as habilidades de comunicação dos enfermeiros do grupo experimental.


Subject(s)
Humans , Male , Female , Communication , Self Efficacy , Education , Nurses, Male
2.
Int J Emerg Med ; 17(1): 13, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38287277

ABSTRACT

BACKGROUND: Pre-hospital trauma life support (PHTLS) training courses have been developed and widely adopted to enhance the proficiency of pre-hospital personnel in handling trauma patients. The objective of this study was to assess the effectiveness of the educational program for managing trauma patients in the pre-hospital emergency setting, utilizing Kirkpatrick's educational evaluation model. METHODS: This is an observational approach, consisting of four sub-studies. The PHTLS course was conducted over a 2-day period, encompassing both theoretical and practical components. For this study, we selected pre-hospital personnel from three emergency aid stations using a convenient sampling method. These personnel underwent their first-ever PHTLS course training, and we subsequently analyzed the effectiveness of the training program using Kirkpatrick's four levels of evaluation: satisfaction, learning, behavior, and results. RESULTS: The study conducted on Kirkpatrick's first-level analysis revealed that participants expressed a high level of satisfaction with the quality of all aspects of the course. Moving on to the second and third levels, namely learning and behavior, significant improvements were observed in the average scores of various skills that were examined both immediately after the course and 2 months later (P < 0.05). However, when it comes to the fourth level and the impact of the course on indicators such as mortality rate and permanent disability, no significant changes were observed even after an average of 3 months since the course was introduced. CONCLUSION: The implementation of PHTLS has been linked to the enhancement of participants' skills in treating trauma patients, leading to the application of acquired knowledge in real-life scenarios and a positive change in participants' behavior. The evaluation of PHTLS courses in Iran, as in other countries, highlights the need for specialized training in pre-hospital trauma care. To ensure the continued effectiveness of the PHTLS course, it is advisable for managers and policymakers to encourage regular participation of PHTLS employees in the program.

3.
Nat Commun ; 14(1): 5217, 2023 Aug 26.
Article in English | MEDLINE | ID: mdl-37633934

ABSTRACT

Tie strengths in social networks are heterogeneous, with strong and weak ties playing different roles at the network and individual levels. Egocentric networks, networks of relationships around an individual, exhibit few strong ties and more weaker ties, as evidenced by electronic communication records. Mobile phone data has also revealed persistent individual differences within this pattern. However, the generality and driving mechanisms of social tie strength heterogeneity remain unclear. Here, we study tie strengths in egocentric networks across multiple datasets of interactions between millions of people during months to years. We find universality in tie strength distributions and their individual-level variation across communication modes, even in channels not reflecting offline social relationships. Via a simple model of egocentric network evolution, we show that the observed universality arises from the competition between cumulative advantage and random choice, two tie reinforcement mechanisms whose balance determines the diversity of tie strengths. Our results provide insight into the driving mechanisms of tie strength heterogeneity in social networks and have implications for the understanding of social network structure and individual behavior.

4.
Med J Islam Repub Iran ; 35: 96, 2021.
Article in English | MEDLINE | ID: mdl-34956942

ABSTRACT

Background: Clinical faculty development plays a significant role in the professional empowerment of future physicians. Identification of educational needs is an important step in planning faculty development. This study identified the educational needs of medical faculties in the clinical setting. Methods: This cross-sectional needs assessment study was conducted in Iranian medical universities during 2016-2018 using a triangulation paradigm. A total of 384 medical clinical faculties, 54 medical education specialists, and 194 faculty evaluation forms completed by medical residents participated in the study using a convenient randomized sampling method. The data were gleaned with a researcher-made questionnaire with 14 areas developed on the basis of clinical education goals and contexts and were analyzed with SPSS16 using descriptive statistic indices such as mean, standard deviation, and frequency percentile. Analytical tests including independent t-test, chi-square and Cramer's V were also applied (p<0.05). The content validity, face validity, and reliability were approved. Results: The response rate was %59 (227) for clinical faculties, %77 (42) for medical education specialists, and %58 (110) for residents. Professionalism was the first priority of needs from the viewpoint of clinical faculties and faculty development planners. The clinical teachers' highest level skills, in their own perspective and also students' perspective, were procedure training and grand round, whereas their lowest level skills were emotional intelligence and morning report. The greatest gap existed between the current skill and the need is management and leadership in the clinical setting. Cramer's index ranged between 0.18 and 0.34 (p<0.05); hence, there was a correlation between the current status and the announced needs in all subjects. Conclusion: Designers of faculty development programs ought to pay due attention to areas of professionalism, management, and leadership and carry out accurate and comprehensive planning to enable students to become competent future physicians in the roles of therapist, manager, teacher, supporter, and researcher.

5.
Adv Med Educ Pract ; 10: 515-526, 2019.
Article in English | MEDLINE | ID: mdl-31410076

ABSTRACT

INTRODUCTION: Medical faculties are responsible for the training and development of future physicians. Therefore, they must learn the teaching methods. Considering their extensive roles, adult learning theory, and technological developments, the best solution is e-learning. This study extracted the views and preferences of clinical faculties about the electronic faculty development programs. METHODS: Clinical faculty members and medical education and e-learning specialists from medical universities in Iran participated in this qualitative content analysis study during 2017-2018. Data were collected with purposive sampling method by 18 semi-structured interviews and 2 focus groups with 11 participants. The data were analyzed using the conventional qualitative content analysis method. Validity and accuracy of data were provided on the basis of Guba and Lincoln criteria. RESULTS: Five categories including "Technology infrastructure" (Presentation, Platform, E-Learning environment), "learner" (Features, Motivation), "Program management" (Blending, Interaction), "content" (Design, Application, Organization), and "evaluation" (Learner assessment, Program evaluation) were extracted. CONCLUSION: Faculty members prefer to attend e-learning courses that focus on individualization, blended learning, and mobile learning. The best solution is to use the microlearning approach, that is, short pieces of content focusing on a learning goal that can be presented by all electronic devices in the form of any kind of media, and is in fact the learning fingerfood.

6.
Fundam Clin Pharmacol ; 32(4): 392-399, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29512848

ABSTRACT

Metformin (Met) has been shown to have pleiotropic effects such as neuroprotective, antioxidant, and anti-inflammatory properties making that a potential candidate for the treatment of central nervous system (CNS) disorders. This study was designed to investigate the possible effect of Met on the d-galactose (d-gal)-induced aging in ovariectomized mice. The female mice underwent bilateral ovariectomy. d-gal was administered orally at a dose of 500 mg/kg, and Met was administrated orally at doses of 1 and 10 mg/kg for 6 weeks. Anxiety-like behavior was evaluated by the elevated plus-maze. Physical power was assessed by vertical grid holding test and forced swimming capacity test. The brains were assessed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). Ovariectomy caused anxiety and declined the physical power as well as BDNF and SOD levels. d-gal administration in ovariectomized mice exacerbated these deleterious effects. Met hampered the anxiety-like behavior and strengthened the physical power of d-gal-treated ovariectomized mice. Met also increased the SOD and BDNF levels in the brains of d-gal-treated ovariectomized animals. Based on the obtained results, we suggest Met administration as a novel therapeutic approach for the treatment of age-related conditions in the absence of female sex hormones.


Subject(s)
Aging/drug effects , Galactose/pharmacology , Metformin/pharmacology , Aging/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Brain/drug effects , Brain/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Female , Maze Learning/drug effects , Mice , Neuroprotective Agents/pharmacology , Ovariectomy/methods , Superoxide Dismutase/metabolism
7.
Iran J Basic Med Sci ; 21(1): 19-25, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29372032

ABSTRACT

OBJECTIVES: Metformin (Met), an antidiabetic biguanide, reduces hyperglycemia via improving glucose utilization and reducing the gluconeogenesis. Met has been shown to exert neuroprotective, antioxidant and anti-inflammatory properties. The present study investigated the possible effect of Met on the D-galactose (D-gal)-induced aging in mice. MATERIALS AND METHODS: Met (1 and 10 mg/kg/p.o.), was administrated daily in D-gal-received (500 mg/kg/p.o.) mice model of aging for six weeks. Anxiety-like behavior, cognitive function, and physical power were evaluated by the elevated plus-maze, novel object recognition task (NORT), and forced swimming capacity test, respectively. The brains were analyzed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). RESULTS: Met decreased the anxiety-like behavior in D-gal-treated mice. Also, Met treated mice showed significantly improved learning and memory ability in NORT compared to the D-gal-treated mice. Furthermore, Met increased the physical power as well as the activity of SOD and BDNF level in D-gal-treated mice. CONCLUSION: Our results suggest that the use of Met can be an effective strategy for prevention and treatment of D-gal-induced aging in animal models. This effect seems to be mediated by attenuation of oxidative stress and enhancement of the neurotrophic factors.

8.
Appl Netw Sci ; 3(1): 8, 2018.
Article in English | MEDLINE | ID: mdl-30839774

ABSTRACT

The structure of egocentric networks reflects the way people balance their need for strong, emotionally intense relationships and a diversity of weaker ties. Egocentric network structure can be quantified with 'social signatures', which describe how people distribute their communication effort across the members (alters) of their personal networks. Social signatures based on call data have indicated that people mostly communicate with a few close alters; they also have persistent, distinct signatures. To examine if these results hold for other channels of communication, here we compare social signatures built from call and text message data, and develop a way of constructing mixed social signatures using both channels. We observe that all types of signatures display persistent individual differences that remain stable despite the turnover in individual alters. We also show that call, text, and mixed signatures resemble one another both at the population level and at the level of individuals. The consistency of social signatures across individuals for different channels of communication is surprising because the choice of channel appears to be alter-specific with no clear overall pattern, and ego networks constructed from calls and texts overlap only partially in terms of alters. These results demonstrate individuals vary in how they allocate their communication effort across their personal networks and this variation is persistent over time and across different channels of communication.

9.
PLoS One ; 11(12): e0167546, 2016.
Article in English | MEDLINE | ID: mdl-27911929

ABSTRACT

BACKGROUND: Classification of medical sciences into its sub-branches is crucial for optimum administration of healthcare and specialty training. Due to the rapid and continuous evolution of medical sciences, development of unbiased tools for monitoring the evolution of medical disciplines is required. METHODOLOGY/PRINCIPAL FINDINGS: Network analysis was used to explore how the medical sciences have evolved between 1980 and 2015 based on the shared words contained in more than 9 million PubMed abstracts. The k-clique percolation method was used to extract local research communities within the network. Analysis of the shared vocabulary in research papers reflects the trends of collaboration and splintering among different disciplines in medicine. Our model identifies distinct communities within each discipline that preferentially collaborate with other communities within other domains of specialty, and overturns some common perceptions. CONCLUSIONS/SIGNIFICANCE: Our analysis provides a tool to assess growth, merging, splitting and contraction of research communities and can thereby serve as a guide to inform policymakers about funding and training in healthcare.


Subject(s)
Biomedical Research , Vocabulary, Controlled , Humans
10.
PLoS Pathog ; 9(5): e1003395, 2013.
Article in English | MEDLINE | ID: mdl-23737750

ABSTRACT

Viral infections of central nervous system (CNS) often trigger inflammatory responses that give rise to a wide range of pathological outcomes. The CNS is equipped with an elaborate network of innate immune sentinels (e.g. microglia, macrophages, dendritic cells) that routinely serve as first responders to these infections. The mechanisms that underlie the dynamic programming of these cells following CNS viral infection remain undefined. To gain insights into this programming, we utilized a combination of genomic and two-photon imaging approaches to study a pure innate immune response to a noncytopathic virus (lymphocytic choriomeningitis virus) as it established persistence in the brain. This enabled us to evaluate how global gene expression patterns were translated into myeloid cell dynamics following infection. Two-photon imaging studies revealed that innate myeloid cells mounted a vigorous early response to viral infection characterized by enhanced vascular patrolling and a complete morphological transformation. Interestingly, innate immune activity subsided over time and returned to a quasi-normal state as the virus established widespread persistence in the brain. At the genomic level, early myeloid cell dynamics were associated with massive changes in CNS gene expression, most of which declined over time and were linked to type I interferon signaling (IFN-I). Surprisingly, in the absence of IFN-I signaling, almost no differential gene expression was observed in the nervous system despite increased viral loads. In addition, two-photon imaging studies revealed that IFN-I receptor deficient myeloid cells were unresponsive to viral infection and remained in a naïve state. These data demonstrate that IFN-I engages non-redundant programming responsible for nearly all innate immune activity in the brain following a noncytopathic viral infection. This Achilles' heel could explain why so many neurotropic viruses have acquired strategies to suppress IFN-I.


Subject(s)
Gene Expression Regulation , Interferon Type I/metabolism , Lymphocytic Choriomeningitis/metabolism , Lymphocytic choriomeningitis virus/metabolism , Myeloid Cells/metabolism , Nerve Tissue Proteins/biosynthesis , Animals , Interferon Type I/genetics , Lymphocytic Choriomeningitis/genetics , Lymphocytic Choriomeningitis/pathology , Mice , Mice, Knockout , Myeloid Cells/pathology , Nerve Tissue Proteins/genetics , Signal Transduction/genetics
11.
J Exp Med ; 210(4): 757-74, 2013 Apr 08.
Article in English | MEDLINE | ID: mdl-23530125

ABSTRACT

Immune responses to persistent viral infections and cancer often fail because of intense regulation of antigen-specific T cells-a process referred to as immune exhaustion. The mechanisms that underlie the induction of exhaustion are not completely understood. To gain novel insights into this process, we simultaneously examined the dynamics of virus-specific CD8(+) and CD4(+) T cells in the living spleen by two-photon microscopy (TPM) during the establishment of an acute or persistent viral infection. We demonstrate that immune exhaustion during viral persistence maps anatomically to the splenic marginal zone/red pulp and is defined by prolonged motility paralysis of virus-specific CD8(+) and CD4(+) T cells. Unexpectedly, therapeutic blockade of PD-1-PD-L1 restored CD8(+) T cell motility within 30 min, despite the presence of high viral loads. This result was supported by planar bilayer data showing that PD-L1 localizes to the central supramolecular activation cluster, decreases antiviral CD8(+) T cell motility, and promotes stable immunological synapse formation. Restoration of T cell motility in vivo was followed by recovery of cell signaling and effector functions, which gave rise to a fatal disease mediated by IFN-γ. We conclude that motility paralysis is a manifestation of immune exhaustion induced by PD-1 that prevents antiviral CD8(+) T cells from performing their effector functions and subjects them to prolonged states of negative immune regulation.


Subject(s)
Antigens, Differentiation/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Movement/immunology , Lymphocytic Choriomeningitis/immunology , Lymphocytic choriomeningitis virus/immunology , Animals , Antigens, Differentiation/genetics , B7-H1 Antigen/genetics , B7-H1 Antigen/immunology , CD4-Positive T-Lymphocytes/immunology , Cell Movement/genetics , Immunity, Cellular/genetics , Interferon-gamma/genetics , Interferon-gamma/immunology , Lymphocytic Choriomeningitis/genetics , Lymphocytic choriomeningitis virus/genetics , Mice , Mice, Knockout , Programmed Cell Death 1 Receptor , Viral Load/genetics , Viral Load/immunology
12.
J Virol ; 86(13): 7060-71, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22553324

ABSTRACT

Persistent viral infections often overburden the immune system and are a major cause of disease in humans. During many persistent infections, antiviral T cells are maintained in a state of immune exhaustion characterized by diminished effector and helper functions. In mammalian systems, an extensive immune regulatory network exists to limit unwanted, potentially fatal immunopathology by inducing T cell exhaustion. However, this regulatory network at times overprotects the host and fosters viral persistence by severely dampening adaptive immune responsiveness. Importantly, recent studies have shown that T cell exhaustion is mediated in part by host immunoregulatory pathways (e.g., programmed death 1 [PD-1], interleukin 10 [IL-10]) and that therapeutic blockade of these pathways either before or during persistent infection can promote viral clearance. Transforming growth factor beta (TGF-ß) is another immunosuppressive cytokine known to impede both self- and tumor-specific T cells, but its role in regulating antiviral immunity is not entirely understood. In this study, we inhibited TGF-ß with three potent antagonists to determine whether neutralization of this regulatory molecule is a viable approach to control a persistent viral infection. Our results revealed that these inhibitors modestly elevate the number of antiviral T cells following infection with a persistent variant of lymphocytic choriomeningitis virus (LCMV) but have no impact on viral clearance. These data suggest that therapeutic neutralization of TGF-ß is not an efficacious means to promote clearance of a persistent viral infection.


Subject(s)
Arenaviridae Infections/drug therapy , Arenaviridae Infections/immunology , CD8-Positive T-Lymphocytes/immunology , Immunologic Factors/administration & dosage , Lymphocytic choriomeningitis virus/immunology , Transforming Growth Factor beta/antagonists & inhibitors , Animals , Arenaviridae Infections/virology , CD4-Positive T-Lymphocytes/immunology , Chronic Disease , Cytokines/biosynthesis , Disease Models, Animal , Mice , Mice, Inbred C57BL , Mice, Transgenic , Treatment Outcome
13.
J Immunol ; 183(6): 3895-905, 2009 Sep 15.
Article in English | MEDLINE | ID: mdl-19717517

ABSTRACT

Persistence of even the stealthiest viruses can perturb immune function either to the benefit or detriment of the host. Lymphocytic choriomeningitis virus (LCMV) establishes lifelong, systemic persistence when introduced in utero or at birth. Despite a highly evolved host-pathogen relationship, LCMV cannot escape detection by the innate immune system, which results in chronic stimulation of the type 1 IFN pathway in adult carrier mice. In this study we demonstrate that IFN-beta is chronically up-regulated in peripheral lymphoid and nonlymphoid tissues (but not the CNS) of mice persistently infected from birth with LCMV and that dendritic cells (DCs) represent at least one source of IFN-beta. Interestingly, chronic stimulation of this innate pathway significantly elevated MHC class I expression in the CNS as well as the periphery. Elevated MHC I expression was dependent on IFN-alphabeta receptor but not MyD88-dependent signaling, as only genetic deletion of the former reduced MHC I to normal levels. An increase in circulating virus was also observed in the IFN-alphabeta receptor deficient carrier mice, signifying that type I IFN continually exerts anti-viral pressure during a LCMV carrier state. Finally, to determine whether heightened CNS MHC I could be therapeutically corrected, we purged LCMV carrier mice of their persistent infection using adoptive immunotherapy. This treatment significantly reduced CNS MHC I expression. Collectively, these data demonstrate that even a well adapted pathogen can chronically stimulate the innate immune system and consequently alter the expression of Ag presenting machinery in an immunologically specialized compartment like the CNS.


Subject(s)
Central Nervous System/immunology , Histocompatibility Antigens Class I/genetics , Interferon-beta/genetics , Receptor, Interferon alpha-beta/metabolism , Virus Diseases/immunology , Animals , Chronic Disease , Immunotherapy , Lymphocytic choriomeningitis virus/immunology , Mice , Receptor, Interferon alpha-beta/immunology , Up-Regulation , Virus Diseases/therapy
14.
J Virol ; 83(17): 8905-15, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19553326

ABSTRACT

Persistent viral infections are a major health concern worldwide. During persistent infection, overwhelming viral replication and the rapid loss of antiviral T-cell function can prevent immune-mediated clearance of the infection, and therapies to reanimate the immune response and purge persistent viruses have been largely unsuccessful. Adoptive immunotherapy using memory T cells is a highly successful therapeutic approach to eradicate a persistent viral infection. Understanding precisely how therapeutically administered memory T cells achieve clearance should improve our ability to terminate states of viral persistence in humans. Mice persistently infected from birth with lymphocytic choriomeningitis virus are tolerant to the pathogen at the T-cell level and thus provide an excellent model to evaluate immunotherapeutic regimens. Previously, we demonstrated that adoptively transferred memory T cells require recipient dendritic cells to effectively purge an established persistent viral infection. However, the mechanisms that reactivate and sustain memory T-cell responses during clearance of such an infection remain unclear. Here we establish that therapeutic memory T cells require CD80 and CD86 costimulatory signals to efficiently clear an established persistent viral infection in vivo. Early blockade of costimulatory pathways with CTLA-4-Fc decreased the secondary expansion of virus-specific CD8(+) and CD4(+) memory T cells as well as their ability to produce antiviral cytokines and purge the persistent infection. Late costimulation blockade also reduced virus-specific T-cell numbers, illustrating that sustained interactions with costimulatory molecules is required for efficient T-cell expansion. These findings indicate that antiviral memory T cells require costimulation to efficiently clear a persistent viral infection and that costimulatory pathways can be targeted to modulate the magnitude of an adoptive immunotherapeutic regimen.


Subject(s)
Adoptive Transfer , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Immunotherapy/methods , Lymphocytic Choriomeningitis/therapy , Lymphocytic choriomeningitis virus/immunology , Animals , B7-1 Antigen/immunology , B7-2 Antigen/immunology , Lymphocyte Activation/immunology , Mice
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