Alcohol Use Predicts Face Perception Impairments and Difficulties in Face Recognition.

Background: Risky alcohol use is related to a variety of cognitive impairments, including memory and visuo-perceptual difficulties. Remarkably, no prior work has assessed whether usage of alcohol can predict difficulties perceiving facial identity. Objectives: Therefore, this study aimed to investigate whether riskier alcohol consumption predicted impairments in face perception and self-reported difficulties in face recognition. Results: Participants (N = 239, male = 77) were over 18 years old and had normal or corrected-to-normal vision. Alcohol use was assessed using the Alcohol Use Disorder Identification Test (AUDIT), while face recognition difficulties were determined by the 20-item Prosopagnosia Index questionnaire (PI20). A subsample of participants (N = 126, male = 51) completed the Cambridge Face Perception task (CFPT) to assess their face perception ability. Multiple linear regressions showed significant models of prediction on both face perception and face recognition when considering AUDIT score and age as predictors. Conclusion: This study suggested, for the first time, that risky alcohol use predicts both poorer visuo-perceptual processing for faces and self-reported difficulties in face recognition.

An online cognitive bias task: the Rough Estimation Task using Qualtrics.

Measurement of cognitive bias typically relies on laboratory-based tasks. In order for cognitive bias measures to be useful outside of laboratory settings, a simple measure is required which does not rely on precise measurement tools, for example, precise reaction time measurement (which can be done only with specialized software typically running through either dedicated hardware or specifically configured computers). The Rough Estimation Task is a simple reading task which has been previously shown to be an effective measure of alcohol-related cognitive bias. We conducted an online version of the Rough Estimation Task, so that we could measure cognitive bias away from a laboratory environment. We also measured whether baseline Rough Estimation Task scores could predict future drinking and Rough Estimation Task scores. A sample of undergraduate participants completed the study online. We found that the online Rough Estimation Task was associated with both current and future drinking, as measured in a follow-up online task. The results imply that the online Rough Estimation Task could be used as a simple online measure of cognitive bias for both concurrent and future drinking behavior, and so raises hope for employing this measure outside of laboratory settings and possibly even in clinical applications.

Environmental Context Influences Visual Attention to Responsible Drinking Messages.

AIMS: Responsible drinking messages (RDMs) are used as a key tool to reduce alcohol-related harms. A common form of RDM is in a poster format displayed in places such as bars, bus stops and toilet cubicles. However, evidence for the effectiveness of RDMs remains limited. Moreover, it is not known how environmental contexts (e.g. the number of alcohol-related cues in the environment) impact how such RDMs are interacted with, nor how this in turn affects their efficacy. METHODS: One hundred participants completed a pseudo taste preference task in either in a bar laboratory (alcohol cue rich environmental context) or a traditional laboratory. The walls of the laboratory displayed either RDM or control posters during this task and eye tracking was used to assess participant attention to the posters. RESULTS: Participants looked at the RDM posters less in the bar laboratory where the environmental context is rich in alcohol cues compared to a traditional laboratory where alcohol cues are sparse. Neither poster type or environmental context affected the amount of 'alcohol' consumed and the amount of visual attention given to RDMs was unrelated to the amount of 'alcohol' consumed. CONCLUSIONS: These findings provide experimental evidence that RDMs do not influence drinking behaviour in the direction intended (reduced consumption in situ). In addition, locating RDMs in alcohol-cue rich environments may result in sub-optimal behavioural responses to the RDM materials (e.g. visual attention to content). To maximize the potential impact of RDMs, the optimal location for RDMs is in environments where pre-existing alcohol cues are sparse to non-existent. SHORT SUMMARY: Responsible drinking messages (RDMs) aim to reduce alcohol consumption, however, the findings of this study show that they may not influence in situ consumption. These findings also suggest that the optimal location for RDMs is in environments with few or no other alcohol-related cues.

Alginate oligosaccharides modify hyphal infiltration of Candida albicans in an in vitro model of invasive human candidosis.

AIMS: A novel alginate oligomer (OligoG CF-5/20) has been shown to potentiate antifungal therapy against a range of fungal pathogens. The current study assessed the effect of this oligomer on in vitro virulence factor expression and epithelial invasion by Candida species. METHODS AND RESULTS: Plate substrate assays and epithelial models were used to assess Candida albicans (CCUG 39343 and ATCC 90028) invasion, in conjunction with confocal laser scanning microscopy and histochemistry. Expression of candidal virulence factors was determined biochemically and by quantitative PCR (qPCR). Changes in surface charge of C. albicans following OligoG treatment were analysed using electrophoretic light scattering. OligoG induced marked alterations in hyphal formation in the substrate assays and reduced invasion in the epithelial model (P < 0·001). Significant dose-dependent inhibition of phospholipase activity in C. albicans was evident following OligoG treatment (P < 0·05). While OligoG binding failed to affect alterations in surface charge (P > 0·05), qPCR demonstrated a reduction in phospholipase B (PLB2) and SAPs (SAP4 and SAP6) expression. CONCLUSION: OligoG CF-5/20 reduced in vitro virulence factor expression and invasion by C. albicans. SIGNIFICANCE AND IMPACT OF THE STUDY: These results, and the previously described potentiation of antifungal activity, define a potential therapeutic opportunity in the treatment of invasive candidal infections.

How cognitive biases can distort environmental statistics: introducing the rough estimation task.

The purpose of this study was to develop a novel behavioural method to explore cognitive biases. The task, called the Rough Estimation Task, simply involves presenting participants with a list of words that can be in one of three categories: appetitive words (e.g. alcohol, food, etc.), neutral related words (e.g. musical instruments) and neutral unrelated words. Participants read the words and are then asked to state estimates for the percentage of words in each category. Individual differences in the propensity to overestimate the proportion of appetitive stimuli (alcohol-related or food-related words) in a word list were associated with behavioural measures (i.e. alcohol consumption, hazardous drinking, BMI, external eating and restrained eating, respectively), thereby providing evidence for the validity of the task. The task was also found to be associated with an eye-tracking attentional bias measure. The Rough Estimation Task is motivated in relation to intuitions with regard to both the behaviour of interest and the theory of cognitive biases in substance use.

Phylogenetic turnover along local environmental gradients in tropical forest communities.

While the importance of local-scale habitat niches in shaping tree species turnover along environmental gradients in tropical forests is well appreciated, relatively little is known about the influence of phylogenetic signal in species' habitat niches in shaping local community structure. We used detailed maps of the soil resource and topographic variation within eight 24-50 ha tropical forest plots combined with species phylogenies created from the APG III phylogeny to examine how phylogenetic beta diversity (indicating the degree of phylogenetic similarity of two communities) was related to environmental gradients within tropical tree communities. Using distance-based redundancy analysis we found that phylogenetic beta diversity, expressed as either nearest neighbor distance or mean pairwise distance, was significantly related to both soil and topographic variation in all study sites. In general, more phylogenetic beta diversity within a forest plot was explained by environmental variables this was expressed as nearest neighbor distance versus mean pairwise distance (3.0-10.3 % and 0.4-8.8 % of variation explained among plots, respectively), and more variation was explained by soil resource variables than topographic variables using either phylogenetic beta diversity metric. We also found that patterns of phylogenetic beta diversity expressed as nearest neighbor distance were consistent with previously observed patterns of niche similarity among congeneric species pairs in these plots. These results indicate the importance of phylogenetic signal in local habitat niches in shaping the phylogenetic structure of tropical tree communities, especially at the level of close phylogenetic neighbors, where similarity in habitat niches is most strongly preserved.

Dyslexia and Substance Use in a University Undergraduate Population.

BACKGROUND: A number of cognitive deficits are associated with dyslexia. However, only a limited amount of research has been performed exploring a putative link between dyslexia and substance use. As substance use is thought to involve a cognitive component, it is possible that the pattern of substance use would be different for dyslexic participants, when compared to nondyslexic controls. During the current study, a guiding hypothesis was that people with dyslexia would demonstrate less substance use than nondyslexic controls. Theories of memory activation, automaticity, and attentional bias in substance use suggest that cognitive components of substance use are important in the development and maintenance of continued substance use and it is thought that, at least some of these components, would be impaired in a dyslexic population. OBJECTIVES: If the cognitive deficits displayed by dyslexics somehow impair the development of cognitive components of substance use, substance use for dyslexic participants may be less pronounced. This paper therefore examines this hypothesis by comparing substance use within dyslexic and nondyslexic participants, from an undergraduate population. METHODS: This was an exploratory questionnaire-based study. Dyslexic participants (n = 35) were compared to control participants (n = 62) on a series of questions designed to measure their substance use history. RESULTS: The results provided preliminary evidence of a difference between dyslexic and nondyslexic substance use. Dyslexics reported a substance use history that was significantly lower than nondyslexic controls. CONCLUSIONS/IMPORTANCE: These results are interpreted in terms of cognitive deficits within dyslexia and with reference to the cognitive model of substance use.

Could Alcohol-Related Cognitive Decline Be the Result of Iron-Induced Neuroinflammation?

Excessive and prolonged alcohol use can have long-term severe neurological consequences. The mechanisms involved may be complicated; however, new evidence seems to indicate the involvement of iron accumulation and neuroinflammation. Prolonged alcohol consumption has been linked to the accumulation of iron in specific regions of the brain. Evidence suggests that excess iron in the brain can trigger microglia activation in response. This activation leads to the release of pro-inflammatory cytokines and reactive oxygen species, which can cause damage to neurons and surrounding brain tissue. Additionally, iron-induced oxidative stress and inflammation can disrupt the blood-brain barrier, allowing immune cells from the periphery to infiltrate the brain. This infiltration can lead to further neuroinflammatory responses. Inflammation in the brain subsequently disrupts neuronal networks, impairs synaptic plasticity, and accelerates neuronal cell death. Consequently, cognitive functions such as memory, attention, and decision-making are compromised. Additionally, chronic neuroinflammation can hasten the development and progression of neurodegenerative diseases, further exacerbating cognitive impairment. Therefore, alcohol could act as a trigger for iron-induced neuroinflammation and cognitive decline. Overall, the mechanisms at play here seem to strongly link alcohol with cognitive decline, with neuroinflammation resulting from alcohol-induced iron accumulation playing a pivotal role.

Are alcohol-related attentional biases and holistic perception independent processes?

Excessive alcohol consumption is associated with the development of attentional biases for alcohol-related cues and their prioritization in heavy drinkers. Recently, it has been hypothesized that holistic processing may also play a role in this prioritization, with higher alcohol consumers exhibiting stronger holistic perception for alcohol cues. However, it is unclear how processing stimuli holistically may be related to attentional biases. We explored potential relationships between attentional biases, holistic processing, and alcohol consumption in a sample of drinkers using two tasks. In the first, a visual probe task replicated previous findings by showing an increased attentional bias for alcohol-related stimuli in individuals with higher alcohol consumption. Surprisingly, using an inversion paradigm to measure holistic perception in our second task, we showed reduced holistic processing for both alcohol and nonalcohol cues in higher alcohol consumers compared to light alcohol consumers. Although alcohol consumption was positively associated with attentional biases and negatively associated with holistic processing, these cognitive processes were not associated with each other. This study supports a model of visual perception in which attentional biases and holistic processing are independently linked with alcohol use. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Habitat filtering across tree life stages in tropical forest communities.

Tropical tree communities are shaped by local-scale habitat heterogeneity in the form of topographic and edaphic variation, but the life-history stage at which habitat associations develop remains poorly understood. This is due, in part, to the fact that previous studies have not accounted for the widely disparate sample sizes (number of stems) that result when trees are divided into size classes. We demonstrate that the observed habitat structuring of a community is directly related to the number of individuals in the community. We then compare the relative importance of habitat heterogeneity to tree community structure for saplings, juveniles and adult trees within seven large (24-50 ha) tropical forest dynamics plots while controlling for sample size. Changes in habitat structuring through tree life stages were small and inconsistent among life stages and study sites. Where found, these differences were an order of magnitude smaller than the findings of previous studies that did not control for sample size. Moreover, community structure and composition were very similar among tree sub-communities of different life stages. We conclude that the structure of these tropical tree communities is established by the time trees are large enough to be included in the census (1 cm diameter at breast height), which indicates that habitat filtering occurs during earlier life stages.

The Effectiveness of Home-Based Exergames Training on Cognition and Balance in Older Adults: A Comparative Quasi-Randomized Study of Two Exergame Interventions.

Background and Objectives: The effectiveness of exergames on fall risk and related physical and cognitive function in older adults is still unclear, with conflicting findings. The discrepancy in these results could be due to the different components and task-specific demands of individual exergame interventions. This open-label quasi-randomized study aimed to compare the efficacy of 2 different home-based dual-task exergame treatments on cognition, mobility, and balance in older people. Research Design and Methods: Fifty older adults (65-85 years of age) were allocated to one of two 8-week exergame interventions: Cognitive-Intensive Exergame Training (CIT) or Physical-Intensive Exergame Training (PIT). Cognitive functions, balance, and mobility were assessed at baseline and after 8 weeks. Group × time interaction was measured by repeated-measure ANOVA, and both intention-to-treat (ITT) and per-protocol (PP) analyses were performed to assess the effectiveness of exergame interventions. Results: ITT analyses showed that improvement in visual processing speed and visuospatial working memory was greater in the CIT group, with a medium effect size (p = .04; η2 = 0.09 and p = .01; η2 = 0.12). The improvement in verbal memory and attention was significant within both groups (p < .05), but this improvement was not different between the groups (p > .05). A significant improvement in balance was also observed in the PIT group, with a medium effect size (p = .04; η2 = 0.09). Although mobility improved significantly in both groups (p < .01), there was no significant difference between groups (p = .08). These results were largely supported by the PP analysis. Discussion and Implications: Dual-task exergame training can improve mobility and cognition in older adults. However, the different cognitive and physical demands of these interventions may have varying impacts on fall risk and related physical or cognitive functions. Therefore, a training program that includes both cognitive and physical domains with appropriate intensity is essential for the development of tailored exergame interventions to reduce fall risk in older adults.

Specific protease activity indicates the degree of Pseudomonas aeruginosa infection in chronic infected wounds.

Chronic non-healing wounds are a major health problem with resident bacteria strongly implicated in their impaired healing. A rapid-screen to provide detailed knowledge of wound bacterial populations would therefore be of value and help prevent unnecessary and indiscriminate use of antibiotics-a process associated with promoting antibiotic resistance. We analysed chronic wound fluid samples, which had been assessed for microbial content, using 20 different fluorescent labelled peptide substrates to determine whether protease activity correlated with the bacterial load. Eight of the peptide substrates showed significant release of fluorescence after reaction with some of the wound samples. Comparison of wound fluid protease activities with the microbiological data indicated that there was no correlation between bacterial counts and enzyme activity for most of the substrates tested. However, two of the peptide substrates produced a signal corresponding with the microbial data revealing a strong positive correlation with Pseudomonas aeruginosa numbers. This demonstrated that short fluorescent labelled peptides can be used to detect protease activity in chronic wound fluid samples. The finding that two peptides were specific indicators for the presence of P. aeruginosa may be the basis for a diagnostic test to determine wound colonisation by this organism.

Toward In-Field Determination of Nitrate Concentrations Via Diffusive Gradients in Thin Films-Incorporation of Reductants and Color Reagents.

Diffusive gradients in thin films (DGTs) have been established as useful tools for the determination of nitrate, phosphate, trace metals, and organic concentrations. General use of DGTs, however, is limited by the subsequent requirement for laboratory analysis. To increase the uptake of DGT as a tool for routine monitoring by nonspecialists, not researchers alone, methods for in-field analysis are required. Incorporation of color reagents into the binding layer, or as the binding layer, could enable the easy and accurate determination of analyte concentrations in-field. Here, we sought to develop a chitosan-stabilized silver nanoparticle (AuNP) suspension liquid-binding layer which developed color on exposure to nitrite, combined with an Fe(0)-impregnated poly-2-acrylamido-2-methyl-1-propanesulfonic acid/acrylamide copolymer hydrogel [Fe(0)-p(AMPS/AMA)] for the reduction of nitrate. The AuNP-chitosan suspension was housed in a 3D designed and printed DGT base, with a volume of 2 mL, for use with the standard DGT solution probe caps. A dialysis membrane with a molecular weight cutoff of <15 kDa was used, as part of the material diffusion layer, to ensure that the AuNP-chitosan did not diffuse through to the bulk solution. This synthesized AuNP-chitosan provided quantitative nitrite concentrations (0 to 1000 mg L-1) and masses (145 µg) in laboratory-based color development studies. An Fe(III)-impregnated poly-2-acrylamido-2-methyl-1-propanesulfonic acid/acrylamide copolymer hydrogel [Fe(III)-p(AMPS/AMA)] was developed (10% AMPS, and 90% AMA), which was treated with NaBH4 to form an Fe(0)-p(AMPS/AMA) hydrogel. The Fe(0)-p(AMPS/AMA) hydrogel quantitatively reduced nitrate to nitrite. The total nitrite mass produced was ∼110 µg, from nitrate. The diffusional characteristics of nitrite and nitrate through the Fe(III)-p(AMPS/AMA) and dialysis membrane were 1.40 × 10-5 and 1.40 × 10-5 and 5.05 × 10-6 and 5.15 × 10-6 cm2 s-1 at 25 °C respectively. The Fe(0)-hydrogel and AuNP-chitosan suspension operated successfully in laboratory tests individually; however, the combined AuNP-chitosan suspension and Fe(0)-hydrogel DGT did not provide quantitative nitrate concentrations. Further research is required to improve the reaction rate of the AuNP-chitosan nitrite-binding layer, to meet the requirement of rapid binding to operate as a DGT.

In vitro interaction of chronic wound bacteria in biofilms.

OBJECTIVE: To use in vitro biofilm models of wound bacterial isolates and compare the biofilms produced for different combinations of wound bacterial species. METHOD: In vitro biofilms, generated by Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus oralis and Micrococcus luteus in microtitre plates and a constant depth film fermentor (CDFF), were studied. The tested isolates all originated from chronic venous leg ulcers. Biofilms of individual and dual combinations of these species were generated in microtitre plate wells at 37°C for 24-96 hours and also in the CDFF for 7 days. The extent of biofilm formation from these systems was then measured using crystal violet staining and/or total viable counts. RESULTS: All the chronic wound bacteria formed biofilms (both individually and in mixed culture) in these models. In mixed species microtitre plate biofilms, both P. aeruginosa and S. aureus appeared to antagonise biofilm formation by S. oralis and M. luteus, with P. aeruginosa completely inhibiting the growth of these organisms. Similar effects were evident in the CDFF model, when all four bacterial species were added simultaneously, with M. luteus being 'out-competed' by the other organisms present and occurring at numbers at the limits of detection; however, there was an apparent increase in the numbers of S. oralis compared with its single culture equivalent. CONCLUSION: The study highlighted differences in biofilm formation ability for the tested species in both closed and open model systems. Using dual species biofilms, distinct species antagonism was observed with apparent antagonism of pathogenic species over 'commensal' ones. Such a finding provides insight into possible bacterial interactions during development of 'non-healing' wound biofilms.

Implementation of early management of iron deficiency in pregnancy during the SARS-CoV-2 pandemic.

Iron deficiency is the commonest cause for anaemia worldwide making it a formidable issue particularly during pregnancy because of increased iron demands. This study looked at establishing a lower limit of normal for haemoglobin concentration (Hb) in our population and to proactively address potentially symptomatic iron deficiency during the current SARS-CoV-2 pandemic. The lower limit of normal for Hb in our 1715 first trimester pregnancy cohort was 116 g/L. This is in contrast with guidance suggesting Hb levels down to 110 g/L are normal. In addition there was evidence of limited testing performed to look for iron deficiency with only 18 % having a serum ferritin checked. Most anaemia was normocytic suggesting that microcytosis is only a late marker of iron deficiency lacking sensitivity. A strategy to avoid hospital contact during the COVID-19 pandemic is proposed.

Development of bromide-selective Diffusive Gradients in Thin-Films for the measurement of average flow rate of streams.

Diffusive Gradients in Thin-Films (DGT) have traditionally been used to measure time-weighted average concentration in water. We tested whether Br--DGT in combination with the trace-dilution flow rate method, could be used as a new approach for measuring water flow rate. A novel bromide selective DGT based on the Purolite Bromide Plus anion exchange resin (Br--DGT) was developed, which provided environmental bromide concentrations comparable to grab samples. The Br--DGT provided quantitative bromide concentrations at a range of pH, competing ion concentrations, and in synthetic natural solution. The uptake efficiency was 95.7 ± 3.4%, and the elution efficiency was 95.5 ± 4.7%. The absorption maximum/saturation point of each binding disk was 0.684 ± 0.001 mg. Bromide adsorption to the binding layer was linear to 44.1% of the total binding capacity, 0.302 mg. The determined diffusion coefficient through the agarose cross-linked polyacrylamide (APA) hydrogels was 1.05 × 10-5 cm2 s-1 at 17.9 °C, temperature corrected to 25 °C was 1.29 × 10-5 cm2 s-1. DGT flow rates were between -14.7 and 6.50% of the flow independently monitored flow rate (weir). In comparison, grab sample flow rates diverged by 5.52 to 58.9% from the weir flow rate.

Top-down and bottom-up attentional biases for smoking-related stimuli: Comparing dependent and non-dependent smokers.

INTRODUCTION: Substance use causes attentional biases for substance-related stimuli. Both bottom-up (preferential processing) and top-down (inhibitory control) processes are involved in attentional biases. We explored these aspects of attentional bias by using dependent and non-dependent cigarette smokers in order to see whether these two groups would differ in terms of general inhibitory control, bottom-up attentional bias, and top-down attentional biases. This enables us to see whether consumption behaviour would affect these cognitive responses to smoking-related stimuli. METHODS: Smokers were categorised as either dependent (N = 26) or non-dependent (N = 34) smokers. A further group of non-smokers (N = 32) were recruited to act as controls. Participants then completed a behavioural inhibition task with general stimuli, a smoking-related eye tracking version of the dot-probe task, and an eye-tracking inhibition task with smoking-related stimuli. RESULTS: Results indicated that dependent smokers had decreased inhibition and increased attentional bias for smoking-related stimuli (and not control stimuli). By contrast, a decreased inhibition for smoking-related stimuli (in comparison to control stimuli) was not observed for non-dependent smokers. CONCLUSIONS: Preferential processing of substance-related stimuli may indicate usage of a substance, whereas poor inhibitory control for substance-related stimuli may only emerge if dependence develops. The results suggest that how people engage with substance abuse is important for top-down attentional biases.

Pupil dilation reflects the authenticity of received nonverbal vocalizations.

The ability to infer the authenticity of other's emotional expressions is a social cognitive process taking place in all human interactions. Although the neurocognitive correlates of authenticity recognition have been probed, its potential recruitment of the peripheral autonomic nervous system is not known. In this work, we asked participants to rate the authenticity of authentic and acted laughs and cries, while simultaneously recording their pupil size, taken as proxy of cognitive effort and arousal. We report, for the first time, that acted laughs elicited higher pupil dilation than authentic ones and, reversely, authentic cries elicited higher pupil dilation than acted ones. We tentatively suggest the lack of authenticity in others' laughs elicits increased pupil dilation through demanding higher cognitive effort; and that, reversely, authenticity in cries increases pupil dilation, through eliciting higher emotional arousal. We also show authentic vocalizations and laughs (i.e. main effects of authenticity and emotion) to be perceived as more authentic, arousing and contagious than acted vocalizations and cries, respectively. In conclusion, we show new evidence that the recognition of emotional authenticity can be manifested at the level of the autonomic nervous system in humans. Notwithstanding, given its novelty, further independent research is warranted to ascertain its psychological meaning.

Nature of the antigenic complex recognized by T lymphocytes. I. Analysis with an in vitro primary response to soluble protein antigens.

In order to analyze the genetic factors involved in the regulation of macrophage-T-cells interaction we have developed an in vitro primary response to soluble protein antigens in which nonimmune guinea pig T cells can be sensitized and subsequently challenged in tissue culture with antigen-pulsed macrophages. Antigen-specific T-cell activation, as measured by increased DNA synthesis, occurred when syngeneic antigen-pulsed macrophages were used for both initial sensitization and secondary challenge. No T-cell activation occurred when allogeneic antigen-pulsed macrophages were used for secondary challenge of cells primed when syngeneic macrophages. When allogeneic antigen-pulsed macrophages were used in both primary and secondary cultures it was difficult to assess antigen-specific stimulation due to the substantial mixed leukocyte reaction. However, when T cells from F1 animals were primed with parental antigen-pulsed macrophages they responded only to the parental macrophages used for initial sensitization but not to those of the other parent. These results are discussed with respect to T-cell recognition of a complex antigenic determinant which may include I-region gene products.

Nature of the antigenic complex recognized by T lymphocytes II. T-cell activation by direct modification of macrophage histocompatibility antigens.

In order to analyze the molecular structures involved in T-cell recognition we developed an in vitro primary response against alloantisera bound to histocompatibility antigens in which nonimmune guinea pig T cells can be sensitized and subsequently challenged in tissue culture with antisera-treated macrophages. If macrophages were incubated with alloantisera directed against the I-region-associated (Ia) antigens of the guinea pig major histocompatibility complex (MHC) T cells could be sensitized to the antisera bound to macrophage Ia determinants. Anti-Ia-treated syngeneic macrophages in the first and second cultures elicited specific T-cell activation, as measured by increased DNA synthesis, to the antisera-induced immunogenic determinants. Similarly, antiIa-treated allogeneic macrophages also specifically stimulated T cells to antisera bound to allogeneic Ia determinants while reducing the mixed leukocyte reaction. Antisera to the B.1 antigens of the guinea pig MHC, the homologue of the mouse H-2K or H-2D antigens, also elicited specific T-cell activation that did not cross-react with that produced by the anti-Ia alloantisera. Furthermore, the anti-B.1-induced stimulation appeared to be associated with the Ia antigens of the macrophage used for priming since (2 x 13)F1 T cells sensitized with anti-B.1-treated parental macrophages could be restimulated only with the parental macrophage used for initial sensitization, and not with those of the other parent. Since the parental strain 2 and strain 13 guinea pigs express serologically identical B.1 antigens and differ only by Ia antigens of the MHC, this observation suggests that both B.1 and Ia antigens may be included in the immunogenic complex recognized by T cells. However, we cannot rule out the possibility that this restriction is due to other genetic differences between strain 2 and strain 13 guinea pigs that is unrelated to the I-region. We interpret these findings as showing that macrophage Ia antigens may serve to directly present antigens bound to the Ia molecule, and possibly indirectly aid in the presentation of antigens bound to other membrane components, such as the B.1 antigens.