Novel roles for IL-15 in T cell survival

Interleukin-15 (IL-15) is generally considered to be a regulator of T cell homeostasis because it works with other common gamma-chain cytokines like IL-2 and IL-7 to control the maintenance of naive and memory T cell populations. However, recent reports highlight new roles for IL-15 during the primary immune responses that involve promoting the survival of antigen-specific CD8+ T cells. These findings illuminate a previously unanticipated role for IL-15 in the generation and resolution of the effector CD8+ T cell response to pathogens

An Application of the Complier Average Causal Effect Analysis to Examine the Effects of a Family Intervention in Reducing Illicit Drug Use among High‐Risk Hispanic Adolescents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107494/1/famp12068.pd

Muscle Strength, Oxygen Saturation and Physical Activity in Patients with Chronic Exertional Compartment Syndrome Compared to Asymptomatic Controls

# Background One of the most common causes of exercise-induced pain in the lower leg is chronic exertional compartment syndrome (CECS). Research is limited on muscle strength, oxygen saturation and physical activity in patients with CECS. # Purpose To compare muscle strength, oxygen saturation, and daily physical activity between patients with CECS and matched asymptomatic controls. A secondary purpose was to investigate the association between oxygen saturation and lower leg pain in patients with CECS. # Study Design Case-control study. # Method Maximal isometric muscle strength of the ankle plantar and dorsiflexors was tested in patients with CECS and sex- and age-matched controls using an isokinetic dynamometer and oxygen saturation (StO~2~) during running was tested by near infrared spectroscopy. Perceived pain and exertion were measured during the test using the Numeric Rating Scale and Borg Rating of Perceived Exertion scale and the exercise-induced leg pain questionnaire. Physical activity was assessed by accelerometry. # Results Twenty-four patients with CECS and 24 controls were included. There were no differences in maximal isometric plantar or dorsiflexion muscle strength between patients and controls. Baseline StO~2~ was 4.5pp (95% CI: 0.7;8.3) lower for patients with CECS than for controls, whereas no difference existed when they experienced pain or reached exhaustion. No differences were found in daily physical activities, except that on average, patients with CECS spent less time cycling daily. During the StO~2~ measurement, patients experienced pain or reached exhaustion while running significantly earlier than the controls (p<0.001). StO~2~ was not associated with leg pain. # Conclusion Patients with CECS have similar leg muscle strength, oxygen saturation and physical activity levels as asymptomatic controls. However, patients with CECS experienced significantly higher levels of lower leg pain than the controls during running, daily activities and at rest. Oxygen saturation and lower leg pain were not associated. # Level of Evidence Level 3b

Cross reactive cellular immune responses in chickens previously exposed to low pathogenic avian influenza

<p>Abstract</p> <p>Background</p> <p>Avian influenza (AI) infection in poultry can result in high morbidity and mortality, and negatively affect international trade. Because most AI vaccines used for poultry are inactivated, our knowledge of immunity against AI is based largely on humoral immune responses. In fact, little is known about cellular immunity following a primary AI infection in poultry, especially regarding cytotoxic T lymphocytes (CTL’s).</p> <p>Methods</p> <p>In these studies, major histocompatibility complex (MHC)-defined (B²/B²) chickens were infected with low pathogenic AI (LPAI) H9N2 and clinical signs of disease were monitored over a two weeks period. Splenic lymphocytes from infected and naïve birds were examined for cross reactivity against homologous and heterologous (H7N2) LPAI by ex vivo stimulation. Cellular immunity was determined by cytotoxic lysis of B²/B² infected lung target cells and proliferation of T cells following exposure to LPAI.</p> <p>Results</p> <p>Infection with H9N2 resulted in statistically significant weight loss compared to sham-infected birds. Splenic lymphocytes derived from H9N2-infected birds displayed lysis of both homologous (H9N2) and heterologous (H7N2) infected target cells, whereas lymphocytes obtained from sham-infected birds did not. T cell proliferation was determined to be highest when exposed to the homologous virus.</p> <p>Conclusions</p> <p>Taken together these data extend the findings that cellular immunity, including CTL’s, is cross reactive against heterologous isolates of AI and contribute to protection following infection.</p

Is Fun For Wellness Engaging? Evaluation of User Experience of an Online Intervention to Promote Well-Being and Physical Activity

Online well-being interventions demonstrate great promise in terms of both engagement and outcomes. Fun For Wellness (FFW) is a novel online intervention grounded in self-efficacy theory and intended to improve multidimensional well-being and physical activity through multi-modal methods. These strategies include capability-enhancing opportunities, learning experiences such as games, video vignettes, and self-assessments. RCT studies have suggested that FFW is efficacious in improving subjective and domain-specific well-being, and effective in improving mental health, physical health, physical activity, and self-efficacy in United States. adults who are overweight and in the general population. The present study uses qualitative and quantitative user experience data collected during two RCT trials to understand and evaluate engagement with FFW, its drivers, and its outcomes. Results suggest that FFW is enjoyable, moderately engaging, and easy to use; and contributes to positive outcomes including skill development and enhanced confidence, for both overweight individuals and the general adult population. Drivers of engagement appear to include rewards, gamification, scenario-based learning, visual tracking for self-monitoring, ease of use and simple communications, and the entertaining, interactive nature of program activities. Findings indicate that there are opportunities to streamline and simplify the experience. These results can help improve FFW and contribute to the science of engagement with online interventions designed to improve well-being

Antiviral CD8+ T cell effector activities in situ are regulated by target cell type

In the lungs of mice infected with influenza, the activity of cytotoxic T lymphocytes is modulated by the type of target cell encountered

Inflammatory chemokine receptors regulate CD8+ T cell contraction and memory generation following infection

CD8+ T cells lacking CXCR3 and CCR5 expression have impaired contraction and generate an increased number of memory cells after virus infection

Identification of a Dual-Specific T Cell Epitope of the Hemagglutinin Antigen of an H5 Avian Influenza Virus in Chickens

Avian influenza viruses (AIV) of the H5N1 subtype have caused morbidity and mortality in humans. Although some migratory birds constitute the natural reservoir for this virus, chickens may play a role in transmission of the virus to humans. Despite the importance of avian species in transmission of AIV H5N1 to humans, very little is known about host immune system interactions with this virus in these species. The objective of the present study was to identify putative T cell epitopes of the hemagglutinin (HA) antigen of an H5 AIV in chickens. Using an overlapping peptide library covering the HA protein, we identified a 15-mer peptide, H5246–260, within the HA1 domain which induced activation of T cells in chickens immunized against the HA antigen of an H5 virus. Furthermore, H5246–260 epitope was found to be presented by both major histocompatibility complex (MHC) class I and II molecules, leading to activation of CD4+ and CD8+ T cell subsets, marked by proliferation and expression of interferon (IFN)-γ by both of these cell subsets as well as the expression of granzyme A by CD8+ T cells. This is the first report of a T cell epitope of AIV recognized by chicken T cells. Furthermore, this study extends the previous finding of the existence of dual-specific epitopes in other species to chickens. Taken together, these results elucidate some of the mechanisms of immune response to AIV in chickens and provide a platform for creation of rational vaccines against AIV in this species

A Single E627K Mutation in the PB2 Protein of H9N2 Avian Influenza Virus Increases Virulence by Inducing Higher Glucocorticoids (GCs) Level

While repeated infection of humans and enhanced replication and transmission in mice has attracted more attention to it, the pathogenesis of H9N2 virus was less known in mice. PB2 residue 627 as the virulent determinant of H5N1 virus is associated with systemic infection and impaired TCR activation, but the impact of this position in H9N2 virus on the host immune response has not been evaluated. In this study, we quantified the cellular immune response to infection in the mouse lung and demonstrate that VK627 and rTsE627K infection caused a significant reduction in the numbers of T cells and inflammatory cells (Macrophage, Neutrophils, Dendritic cells) compared to mice infected with rVK627E and TsE627. Further, we discovered (i) a high level of thymocyte apoptosis resulted in impaired T cell development, which led to the reduced amount of mature T cells into lung, and (ii) the reduced inflammatory cells entering into lung was attributed to the diminished levels in pro-inflammatory cytokines and chemokines. Thereafter, we recognized that higher GCs level in plasma induced by VK627 and rTsE627K infection was associated with the increased apoptosis in thymus and the reduced pro-inflammatory cytokines and chemokines levels in lung. These data demonstrated that VK627 and rTsE627K infection contributing to higher GCs level would decrease the magnitude of antiviral response in lung, which may be offered as a novel mechanism of enhanced pathogenicity for H9N2 AIV

The effector T cell response to influenza infection

Influenza virus infection induces a potent initial innate immune response, which serves to limit the extent of viral replication and virus spread. However, efficient (and eventual) viral clearance within the respiratory tract requires the subsequent activation, rapid proliferation, recruitment, and expression of effector activities by the adaptive immune system, consisting of antibody producing B cells and influenza-specific T lymphocytes with diverse functions. The ensuing effector activities of these T lymphocytes ultimately determine (along with antibodies) the capacity of the host to eliminate the viruses and the extent of tissue damage. In this review, we describe this effector T cell response to influenza virus infection. Based on information largely obtained in experimental settings (i.e., murine models), we will illustrate the factors regulating the induction of adaptive immune T cell responses to influenza, the effector activities displayed by these activated T cells, the mechanisms underlying the expression of these effector mechanisms, and the control of the activation/differentiation of these T cells, in situ, in the infected lungs