CD1d and natural killer T cells in immunity to Mycobacterium tuberculosis.

The critical role of peptide antigen-specific T cells in controlling mycobacterial infections is well documented in natural resistance and vaccine-induced immunity against Mycobacterium tuberculosis. However, many other populations of leukocytes contribute to innate and adaptive immunity against mycobacteria. Among these, non-conventional T cells recognizing lipid antigens presented by the CD1 antigen presentation system have attracted particular interest. In this chapter, we review the basic immunobiology and potential antimycobacterial properties of a subset of CD1-restricted T cells that have come to be known as Natural Killer T cells. This group of lipid reactive T cells is notable for its high level of conservation between humans and mice, thus enabling a wide range of highly informative studies in mouse models. As reviewed below, NKT cells appear to have subtle but potentially significant activities in the host response to mycobacteria. Importantly, they also provide a framework for investigations into other types of lipid antigen-specific T cells that may be more abundant in larger mammals such as humans.

New CD1d agonists: synthesis and biological activity of 6″-triazole-substituted α-galactosyl ceramides.

Huisgen [3+2] dipolar cycloaddition of 6″-azido-6″-deoxy-α-galactosyl ceramide 11 with a range of alkynes (or a benzyne precursor) yielded a series of triazole-containing α-galactosyl ceramide (α-GalCer) analogues in high yield. These α-GalCer analogues and the precursor azide 11 were tested for their ability to activate iNKT cells and stimulate IL-2 cytokine secretion in vitro, and IFN-γ and IL-4 cytokine secretion in vivo. Some of these analogues, specifically 11, 12b, 12f and 13, were more potent IL-2 stimulators than the prototypical CD1d agonist, α-GalCer 1. In terms of any cytokine bias, most of the triazole-containing analogues exhibited a small Th2 cytokine-biasing response relative to that shown by α-GalCer 1. In contrast, the cycloaddition precursor, namely azide 11, provided a small Th1 cytokine-biasing response.

Research or intervention or both? Women's changes after participation in a longitudinal study about intimate partner violence.

INTRODUCTION: The tensions between risk and benefit in research are particularly evident in studies about intimate partner violence. Recalling and relating traumatic experiences may deepen posttraumatic stress or relieve the burden of terrible events long borne in secret. In this article, we examine the effects of study participation in a longitudinal investigation of intimate partner violence using both qualitative and quantitative data. METHOD: Researchers enrolled 200 women in moderately violent intimate relationships and asked them to report about their relationships every day for 12 weeks. Daily, participants telephoned an automated survey and responded to 34 survey questions. They also completed baseline and end-of-study surveys and maintained telephone contact with 1 researcher weekly. Forty-2 participants completed qualitative end-of-study interviews to describe their relationships and their experiences in the study. RESULTS: Over 12 weeks, participants showed improvements in coping strategies, hope, and mental health, and increased readiness to leave their partners. In qualitative interviews, women reported gaining insight, feeling better emotionally, making behavioral changes, finding comfort in daily surveys, learning resources for help, and taking action to improve their lives. Fourteen percent left their partners by end-of-study; 35% sought counseling. DISCUSSION: The study's daily survey invited the participant to become more reflective about her relationship, which changed how she saw herself and her situation. The study methods also included weekly conversations with a compassionate researcher, allowing women to tell their stories. These 2 strategies may be incorporated into brief interventions for intimate partner violence in primary care settings. (PsycINFO Database Record

Coping with intimate partner violence: Qualitative findings from the study of dynamics of husband to wife abuse.

INTRODUCTION: Coping can be defined as an individual's efforts to manage a problem. In Intimate Partner Violence (IPV), coping depends heavily on relationship context, circumstances, and resource availability. The range of coping strategies utilized by women experiencing violence are not fully understood. METHOD: Two hundred female patients who screened positive for verbal or physical abuse were recruited from 6 primary care clinics in San Antonio. Subjects were instructed to complete a baseline survey, which included the COPE scale, as well as daily telephone reports, weekly contact with research staff, and an end-of-study survey. A total of 42 women completed an in-depth qualitative interview at the end of 3 months. RESULTS: Using a template approach to qualitative analysis, interview transcripts were analyzed and coded. "Coping" as a theme emerged independently and was categorized into 14 subcategories, according to the COPE scale; the most commonly endorsed themes from interviews were "avoidance" and "active coping." Previously undescribed methods of coping with IPV were also discovered using this approach, including "preventing escalation" and "ignoring." DISCUSSION: In a qualitative study of women living with IPV, coping emerged as an independent theme. We found that the women used methods not listed on the COPE standardized scale at least as often as more traditional categories. It is important for family medicine clinicians to be aware of the wide variety of coping mechanisms to best address safety planning.

Eosinophils increase neuron branching in human and murine skin and in vitro.

Cutaneous nerves are increased in atopic dermatitis, and itch is a prominent symptom. We studied the functional interactions between eosinophils and nerves in human and mouse skin and in culture. We demonstrated that human atopic dermatitis skin has eosinophil granule proteins present in the same region as increased nerves. Transgenic mice in which interleukin-5 (IL-5) expression is driven by a keratin-14 (K14) promoter had many eosinophils in the epidermis, and the number of nerves was also significantly increased in the epidermis. In co-cultures, eosinophils dramatically increased branching of sensory neurons isolated from the dorsal root ganglia (DRG) of mice. This effect did not occur in DRG neurons co-cultured with mast cells or with dead eosinophils. Physical contact of the eosinophils with the neurons was not required, and the effect was not blocked by an antibody to nerve growth factor. DRG neurons express eotaxin-1, ICAM-1 and VCAM-1, which may be important in the recruitment, binding, and activation of eosinophils in the region of cutaneous nerves. These data indicate a pathophysiological role for eosinophils in cutaneous nerve growth in atopic dermatitis, and suggest they may present a therapeutic target in atopic dermatitis and other eosinophilic skin conditions with neuronal symptoms such as itch.