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Difficulties with pragmatic aspects of communication are universal across individuals with autism spectrum disorders (ASDs). Here we focused on an aspect of pragmatic language comprehension that is relevant to social interaction in daily life: the integration of speaker characteristics inferred from the voice with the content of a message. Using functional magnetic resonance imaging (fMRI), we examined the neural correlates of the integration of voice-based inferences about the speaker’s age, gender or social background, and sentence content in adults with ASD and matched control participants. Relative to the control group, the ASD group showed increased activation in right inferior frontal gyrus (RIFG; Brodmann area 47) for speakerincongruent sentences compared to speaker-congruent sentences. Given that both groups performed behaviourally at a similar level on a debriefing interview outside the scanner, the increased activation in RIFG for the ASD group was interpreted as being compensatory in nature. It presumably reflects spill-over processing from the language dominant left hemisphere due to higher task demands faced by the participants with ASD when integrating speaker characteristics and the content of a spoken sentence. Furthermore, only the control group showed decreased activation for speaker-incongruent relative to speaker-congruent sentences in right ventral medial prefrontal cortex (vMPFC; Brodmann area 10), including right anterior cingulate cortex (ACC; Brodmann area 24/32). Since vMPFC is involved in self-referential processing related to judgments and inferences about self and others, the absence of such a modulation in vMPFC activation in the ASD group possibly points to atypical default self-referential mental activity in ASD. Our results show that in ASD compensatory mechanisms are necessary in implicit, low-level inferential processes in spoken language understanding. This indicates that pragmatic language problems in ASD are not restricted to high-level inferential processes, but encompass the most basic aspects of pragmatic language processing.

PURPOSE. In rats, corneal allograft rejection is delayed for at least 100 days by clodronate liposomes. These liposomes selectively deplete macrophages. To investigate the immunologic basis for absence of graft rejection in treated rats, the effect of these liposomes on the generation of cytotoxic T lymphocytes (CTLs) and antibody production after orthotopic corneal allotransplantation was determined. METHODS. Transplantations of corneal buttons from PVG rats were performed in AO rats. After surgery, one group received clodronate liposomes subconjunctivally at five time points, and the other group remained untreated. On postoperative day (POD) 3, 7, 12, or 17, rats were killed, the presence of CTLs was investigated at three different anatomic locations, and antibodies against donor antigens were tested. RESULTS. NO significant differences were found between the groups tested 3 and 7 days after surgery. But on POD 12 (the time of onset of rejection in the untreated group) and on POD 17, the CTL activities detected in the submandibular lymph nodes (P less than or equal to 0.008) and the spleen (P less than or equal to 0.009) were significantly less in the treated groups compared with the untreated groups. in the untreated groups complement-independent antibodies were present only on POD 17, whereas no antibodies were found in the treated rats. CONCLUSIONS. Local treatment with clodronate liposomes was shown to downregulate local and systemic CTL responses and to prevent the generation of antibodies. Local depletion of macrophages in the initiation phase of the immune response appears to lead to a less vigorous attack on the grafted tissue and therefore to promote graft survival.

Idiopathic inflammation of the cornea, keratitis, has been proposed to result from an autoimmune process, but thus far no convenient animal model of keratitis exists. An attempt was made to establish an animal model for keratitis, to investigate possible autoimmune mechanisms. T-cell lines were established from lymph node cells removed from rats immunized with bovine corneal epithelium (BCE) extract. After restimulation in vitro with BCE or a specific corneal antigen, the cells were transferred by intraperitoneal injection into naive rats, rats subjected to total body irradiation, or rats in which only one eye was irradiated. Neither direct immunization with corneal antigens nor transfer of activated anti-corneal T-cells into naive rats gave any signs of keratitis. Irradiation alone did not induce corneal inflammation. Transfer of corneal-specific activated T cells into irradiated rats produced keratitis starting around day 4 and culminating around day 8. The disease was self-limiting and the severity dependent on the dose and site of radiation. Keratitis was characterized by corneal haze, conjunctival and episcleral hyperemia, episcleral hemorrhages, chemosis, corneal infiltrates, and vascularization. Immunohistochemistry showed T-cell and macrophage infiltration of epithelium and stroma in the affected corneas. Thus, keratitis may be produced by T cells reactive to corneal antigens, provided that the target tissue has been made susceptible by irradiation. The effectiveness of T-cell vaccination in preventing adoptive keratitis suggests that systemic as well as local tissue factors may regulate the disease process