Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as damage-associated molecular patterns or alarmins, remains ill defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8(+) T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a CTL-intrinsic fashion, determined plurifunctional effector cell differentiation, and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses.
4 studies investigated the broad claim that preschoolers understand biological inheritance. In Study 1, 4-7-year-old children were told a story in which a boy was born to one man and adopted by another. The biological father was described as having one set of features (e.g., green eyes) and the adoptive father as having another (e.g., brown eyes). Subjects were asked which man the boy would resemble when he grew up. Preschoolers showed little understanding that selective chains of processes mediate resemblance to parents. It was not until age 7 that children substantially associated the boy with his biological father on physical features and his adoptive father on beliefs. That is, it was not until age 7 that children demonstrated that they understood birth as part of a process selectively mediating the acquisition of physical traits and learning or nurturance as mediating the acquisition of beliefs. In Study 2, subjects were asked whether, as a boy grew up, various of his features could change. Children generally shared our adult intuitions, indicating that their failure in Study 1 was not due to their having a different sense of what features can change. Studies 3 and 4 replicated Study 1, with stories involving mothers instead of fathers and with lessened task demands. Taken together, the results of the 4 studies refute the claim that preschoolers understand biological inheritance. The findings are discussed in terms of whether children understand biology as an autonomous cognitive domain.
Eighty-three 12-month-old infants faced a noisy, active, object for one minute, after which the object turned 45 degrees to the left or the right. Five conditions explored what object features elicited gaze-following behavior in the infants. In one condition, the object was an adult stranger. The other four conditions used a soft, brown, dog-sized, amorphouslyshaped, asymmetrical novel object that varied along two dimensions theorized as central to the identification of intentional beings: facial features and contingently interactive behavior. Infants shifted their own attentional direction to match the orientation of the actor or object in every condition except the one in which the object lacked both a face and contingently interactive behavior. Infants' 'gaze'-following behavior in general, therefore, appears to have been driven selectively by a particular configuration of behavioral and morphological characteristics, specifically those theorized as underlying attributions of intentionality rather than attributions of person per se.
Lymphocytic choriomeningitis virus (LCMV) exhibits natural tropism for dendritic cells and represents the prototypic infection that elicits protective CD8+ T cell (cytotoxic T lymphocyte (CTL)) immunity. Here we have harnessed the immunobiology of this arenavirus for vaccine delivery. By using producer cells constitutively synthesizing the viral glycoprotein (GP), it was possible to replace the gene encoding LCMV GP with vaccine antigens to create replication-defective vaccine vectors. These rLCMV vaccines elicited CTL responses that were equivalent to or greater than those elicited by recombinant adenovirus 5 or recombinant vaccinia virus in their magnitude and cytokine profiles, and they exhibited more effective protection in several models. In contrast to recombinant adenovirus 5, rLCMV failed to elicit vector-specific antibody immunity, which facilitated re-administration of the same vector for booster vaccination. In addition, rLCMV elicited T helper type 1 CD4+ T cell responses and protective neutralizing antibodies to vaccine antigens. These features, together with low seroprevalence in humans, suggest that rLCMV may show utility as a vaccine platform against infectious diseases and cancer.
This paper reviews a recent set of behavioural studies that examine the scope and nature of the representational system underlying theory-of-mind development. Studies with typically developing infants, adults and children with autism all converge on the claim that there is a specialized input system that uses not only morphological cues, but also behavioural cues to categorize novel objects as agents. Evidence is reviewed in which 12- to 15-month-old infants treat certain non-human objects as if they have perceptual/attentional abilities, communicative abilities and goal-directed behaviour. They will follow the attentional orientation of an amorphously shaped novel object if it interacts contingently with them or with another person. They also seem to use a novel object's environmentally directed behaviour to determine its perceptual/attentional orientation and object-oriented goals. Results from adults and children with autism are strikingly similar, despite adults' contradictory beliefs about the objects in question and the failure of children with autism to ultimately develop more advanced theory-of-mind reasoning. The implications for a general theory-of-mind development are discussed.
The present research examined whether infants as young as 6 months of age would consider what objects a human agent could perceive when interpreting her actions on the objects. In two experiments, the infants took the agent's actions of repeatedly reaching for and grasping one of two possible objects as suggesting her preference for that object only when the agent could detect both objects, not when the agent's perceptual access to the second object was absent, either because a large screen hid the object from the agent (Experiment 1), or because the agent sat with her back toward the object (Experiment 2). These results suggest that young infants recognize the role of perception in constraining an agent's goal-actions.
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