Skin resident memory CD8+ T cells are phenotypically and functionally distinct from circulating populations and lack immediate cytotoxic function.

The in-depth understanding of skin resident memory CD8+ T lymphocytes (TRM ) may help to uncover strategies for their manipulation during disease. We investigated isolated TRM from healthy human skin, which expressed the residence marker CD69, and compared them to circulating CD8+ T cell populations from the same donors. There were significantly increased proportions of CD8+ CD45RA- CD27- T cells in the skin that expressed low levels of killer cell lectin-like receptor G1 (KLRG1), CD57, perforin and granzyme B. The CD8+ TRM in skin were therefore phenotypically distinct from circulating CD8+ CD45RA- CD27- T cells that expressed high levels of all these molecules. Nevertheless, the activation of CD8+ TRM with T cell receptor (TCR)/CD28 or interleukin (IL)-2 or IL-15 in vitro induced the expression of granzyme B. Blocking signalling through the inhibitory receptor programmed cell death 1 (PD)-1 further boosted granzyme B expression. A unique feature of some CD8+ TRM cells was their ability to secrete high levels of tumour necrosis factor (TNF)-α and IL-2, a cytokine combination that was not seen frequently in circulating CD8+ T cells. The cutaneous CD8+ TRM are therefore diverse, and appear to be phenotypically and functionally distinct from circulating cells. Indeed, the surface receptors used to distinguish differentiation stages of blood T cells cannot be applied to T cells in the skin. Furthermore, the function of cutaneous TRM appears to be stringently controlled by environmental signals in situ.

A novel processed food classification system applied to Australian food composition databases.

BACKGROUND: The extent of food processing can affect the nutritional quality of foodstuffs. Categorising foods by the level of processing emphasises the differences in nutritional quality between foods within the same food group and is likely useful for determining dietary processed food consumption. The present study aimed to categorise foods within Australian food composition databases according to the level of food processing using a processed food classification system, as well as assess the variation in the levels of processing within food groups. METHODS: A processed foods classification system was applied to food and beverage items contained within Australian Food and Nutrient (AUSNUT) 2007 (n = 3874) and AUSNUT 2011-13 (n = 5740). The proportion of Minimally Processed (MP), Processed Culinary Ingredients (PCI) Processed (P) and Ultra Processed (ULP) by AUSNUT food group and the overall proportion of the four processed food categories across AUSNUT 2007 and AUSNUT 2011-13 were calculated. RESULTS: Across the food composition databases, the overall proportions of foods classified as MP, PCI, P and ULP were 27%, 3%, 26% and 44% for AUSNUT 2007 and 38%, 2%, 24% and 36% for AUSNUT 2011-13. Although there was wide variation in the classifications of food processing within the food groups, approximately one-third of foodstuffs were classified as ULP food items across both the 2007 and 2011-13 AUSNUT databases. CONCLUSIONS: This Australian processed food classification system will allow researchers to easily quantify the contribution of processed foods within the Australian food supply to assist in assessing the nutritional quality of the dietary intake of population groups.

Mediating effects of dietary intake on associations of TV viewing, body mass index and metabolic syndrome in adolescents.

OBJECTIVE: Evidence suggests that TV viewing is associated with body mass index (BMI) and metabolic syndrome (MetS) in adolescents. However, it is unclear whether dietary intake mediates these relationships. METHODS: A cross-sectional analysis was conducted in adolescents (12-19 years) participating in the 2003-2006 United States National Health and Nutrition Examination Survey. BMI z scores (zBMI) (n = 3,161) and MetS (n = 1,379) were calculated using age- and sex-specific criteria for adolescents. TV viewing (h/day) was measured via a self-reported questionnaire, and dietary intake was assessed using two 24-h recalls. Using the MacKinnon method, a series of mediation analyses were conducted examining five dietary mediators (total energy intake, fruit and vegetable intake, discretionary snacks, sugar-sweetened beverages and diet quality) of the relationships between TV viewing and zBMI and MetS. RESULTS: Small positive relationships were observed between TV viewing and zBMI (ß = 0.99, p < 0.001) and TV viewing and MetS (OR = 1.18, p = 0.046). No dietary element appeared to mediate the relationship between TV viewing and zBMI. However, sugar-sweetened beverage consumption and fruit and vegetable intake partially mediated the relationship between TV viewing and MetS, explaining 8.7% and 4.1% of the relationship, respectively. CONCLUSIONS: These findings highlight the complexity of the relationships between TV viewing, dietary intake and cardiometabolic health outcomes, and that TV viewing should remain a target for interventions.

Is the relationship between sedentary behaviour and cardiometabolic health in adolescents independent of dietary intake? A systematic review.

Screen time, but not overall sedentary behaviour, is consistently related to cardiometabolic health in adolescents. Because of the associations screen time has with dietary intake, diet may be an important factor in the screen time and health relationship; however, evidence has not previously been synthesized. Thus, the aim of this systematic review was to explore whether the associations between various sedentary behaviours and cardiometabolic risk markers are independent of dietary intake in adolescents. Online databases and personal libraries were searched for peer-reviewed original research articles published in English before March 2014. Included studies assessed associations between sedentary behaviour and cardiometabolic markers in 12- to 18-year-olds and adjusted for dietary intake. Twenty-five studies met the inclusion criteria. From the 21 studies examining sedentary behaviour and adiposity, the majority found significant positive associations between television viewing, screen time and self-reported overall sedentary behaviour with markers of adiposity, independent of dietary intake. No significant associations between screen time with blood pressure and cholesterol were reported. Sedentary behaviour appears to be associated with adiposity in adolescents, irrespective of dietary intake. However, the variability of dietary variables between studies suggests further work is needed to understand the role of dietary intake when examining these associations in youth.

Investigation of the cutaneous response to recall antigen in humans in vivo.

In this paper we provide a detailed description of an experimental method for investigating the induction and resolution of recall immune response to antigen in humans in vivo. This involves the injection of tuberculin purified protein derivative (PPD) into the skin, followed by inducing suction blisters at the site of injection, from which leucocytes and cytokines that are involved in the response can be isolated and characterized. Using this technique we found that although the majority of CD4(+) T cells in the skin that are present early in the response express cutaneous lymphocyte antigen (CLA), the expression of this marker is reduced significantly in later phases. This may enable these cells to leave the skin during immune resolution. Furthermore, interleukin (IL)-2 production can be detected both in CD4(+) T cells and also in the blister fluid at the peak of the response at day 7, indicating that mediators found in the blister fluid are representative of the cytokine microenvironment in vivo. Finally, we found that older humans have defective ability to respond to cutaneous PPD challenge, but this does not reflect a global immune deficit as they have similar numbers of circulating functional PPD-specific CD4(+) T cells as young subjects. The use of the blister technology enables further characterization of the skin specific defect in older humans and also general mechanisms that govern immune regulation in vivo.

Enhancement of cellular immune response in HIV-1 seropositive individuals: A DNA-based trial.

A DNA-based vaccine containing HIV-1 Env and Rev genes was tested for safety and host immune response in 15 HIV-infected asymptomatic patients with CD4-positive lymphocyte counts >/=500/microl of blood and receiving no antiviral therapy. Successive groups of patients received three doses of vaccine at 30, 100, or 300 microg at 10-week intervals in a dose-escalation trial. Some changes were noted in cytotoxic T-lymphocyte activity against gp160-bearing targets. Importantly, enhanced specific lymphocyte proliferative activity against HIV-1 envelope was observed in multiple patients. Three of three patients in the 300-microg dose group also developed increased MIP-1alpha levels which were detectable in their serum. Interestingly patients in the lowest dose group showed no overall changes in the immune parameters measured. The majority of patients who exhibited increases in any immune parameters were contained within the 300 microg, which was the highest dose group. These studies support further investigation of this technology for the production of antigen-specific immune responses in humans.

First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response.

A DNA-based vaccine containing human immunodeficiency virus type 1 (HIV-1) env and rev genes was tested for safety and host immune response in 15 asymptomatic HIV-infected patients who were not using antiviral drugs and who had CD4+ lymphocyte counts of > or = 500 per microliter of blood. Successive groups received three doses of vaccine (30, 100, or 300 microg) at 10-week intervals in a dose-escalation trial. Vaccine administration induced no local or systemic reactions, and no laboratory abnormalities were detected. Specifically, no patient developed anti-DNA antibody or muscle enzyme elevations. No consistent change occurred in CD4 or CD8 lymphocyte counts or in plasma HIV concentration. Antibody against gp120 increased in individual patients in the 100- and 300-/microg groups. Some increases were noted in cytotoxic T lymphocyte activity against gp160-bearing targets and in lymphocyte proliferative activity. The safety and potential immunogenicity of an HIV-directed DNA-based vaccine was demonstrated, a finding that should encourage further studies.