Prolonged amelioration of acute lung allograft rejection by sequential overexpression of human interleukin-10 and hepatocyte growth factor in rats

The effect of prolonged electroporation-mediated human interleukin-10 (hIL-10) overexpression 24 hours before transplantation, combined with sequential human hepatocyte growth factor (HGF) overexpression into skeletal muscle on day 5, on rat lung allograft rejection was evaluated. Left lung allotransplantation was performed from Brown-Norway to Fischer-F344 rats. Gene transfer into skeletal muscle was enhanced by electroporation. Three groups were studied: group I animals (n = 5) received 2.5 μg pCIK-hIL-10 (hIL-10/CMV [cytomegalovirus] early promoter enhancer) on day -1 and 80 μg pCIK-HGF (HGF/CMV early promoter enhancer) on day 5. Group II animals (n = 4) received 2.5 μg pCIK-hIL-10 and pUbC-hIL-10 (hIL-10/pUbC promoter) on day -1. Control group III animals (n = 4) were treated by sham electroporation on days -1 and 5. All animals received daily nontherapeutic intraperitoneal dose of cyclosporin A (2.5 mg/kg) and were sacrificed on day 15. Graft oxygenation and allograft rejection were evaluated. Significant differences were found between study groups in graft oxygenation (Pao(2)) (P = .0028; group I vs. groups II and III, P < .01 each). Pao(2) was low in group II (31 ± 1 mm Hg) and in group III controls (34 ± 10 mm Hg), without statistically significant difference between these 2 groups (P = .54). In contrast, in group I, Pao(2) of recipients sequentially transduced with IL-10 and HGF plasmids was much improved, with 112 ± 39 mm Hg (vs. groups II and III; P < .01 each), paralleled by reduced vascular and bronchial rejection (group I vs. groups II and III, P < .021 each). Sequential overexpression of anti-inflammatory cytokine IL-10, followed by sequential and overlapping HGF overexpression on day 5, preserves lung function and reduces acute lung allograft rejection up to day 15 post transplant as compared to prolonged IL-10 overexpression alone.

Critical role of regulatory T cells in Th17-mediated minor antigen-disparate rejection

Th17-mediated immune responses have been recently identified as novel pathogenic mechanisms in a variety of conditions; however, their importance in allograft rejection processes is still debated. In this paper, we searched for MHC or minor Ag disparate models of skin graft rejection in which Th17 immune responses might be involved. We found that T cell-derived IL-17 is critical for spontaneous rejection of minor but not major Ag-mismatched skin grafts. IL-17 neutralization was associated with a lack of neutrophil infiltration and neutrophil depletion delayed rejection, suggesting neutrophils as an effector mechanism downstream of Th17 cells. Regulatory T cells (Tregs) appeared to be involved in Th17 reactivity. We found that in vivo Treg depletion prevented IL-17 production by recipient T cells. An adoptive cotransfer of Tregs with naive monospecific antidonor T cells in lymphopenic hosts biased the immune response toward Th17. Finally, we observed that IL-6 was central for balancing Tregs and Th17 cells as demonstrated by the prevention of Th17 differentiation, the enhanced Treg/Th17 ratio, and a net impact of rejection blockade in the absence of IL-6. In conclusion, the ability of Tregs to promote the Th17/neutrophil-mediated pathway of rejection that we have described should be considered as a potential drawback of Treg-based cell therapy.

Behavioral and neural correlates of perceived and imagined musical timbre

The generality of findings implicating secondary auditory areas in auditory imagery was tested by using a timbre imagery task with fMRI. Another aim was to test whether activity in supplementary motor area (SMA) seen in prior studies might have been related to subvocalization. Participants with moderate musical background were scanned while making similarity judgments about the timbre of heard or imagined musical instrument sounds. The critical control condition was a visual imagery task. The pattern of judgments in perceived and imagined conditions was similar, suggesting that perception and imagery access similar cognitive representations of timbre. As expected, judgments of heard timbres, relative to the visual imagery control, activated primary and secondary auditory areas with some right-sided asymmetry. Timbre imagery also activated secondary auditory areas relative to the visual imagery control, although less strongly, in accord with previous data. Significant overlap was observed in these regions between perceptual and imagery conditions. Because the visual control task resulted in deactivation of auditory areas relative to a silent baseline, we interpret the timbre imagery effect as a reversal of that deactivation. Despite the lack of an obvious subvocalization component to timbre imagery, some activity in SMA was observed, suggesting that SMA may have a more general role in imagery beyond any motor component.

Perceived and Imagined Tempos of Familiar Songs

Two studies investigated the similarity of metronome settings to perceived and imagined familiar songs by subjects unselected for musical ability. In Study 1, mean tempo settings in the two tasks were about 100 beats per minute. Songs with slower perceived tempos tended to be faster in the imagery task and vice versa. In Study 2, subjects set fastest and slowest acceptable tempos for the same set of songs in the imagery mode. These settings were positively correlated with the preferred tempo for the song. Most subjects thought that there were limits on how fast or slow a song could be imagined. These results suggest that tempo is explicitly represented in auditory imagery.

CTLA4-Ig Restores Rejection of MHC Class-II Mismatched Allografts by Disabling IL-2-Expanded Regulatory T Cells

Allograft acceptance and tolerance can be achieved by different approaches including inhibition of effector T cell responses through CD28-dependent costimulatory blockade and induction of peripheral regulatory T cells (Tregs). The observation that Tregs rely upon CD28-dependent signals for development and peripheral expansion, raises the intriguing possibility of a counterproductive consequence of CTLA4-Ig administration on tolerance induction. We have investigated the possible negative effect of CTLA4-Ig on Treg-mediated tolerance induction using a mouse model of single MHC class II-mismatched skin grafts in which long-term acceptance was achieved by short-term administration of IL-2/anti-IL-2 complex. CTLA4-Ig treatment was found to abolish Treg-dependent acceptance in this model, restoring skin allograft rejection and Th1 alloreactivity. CTLA4-Ig inhibited IL-2-driven Treg expansion, and prevented in particular the occurrence of ICOS(+) Tregs endowed with potent suppressive capacities. Restoring CD28 signaling was sufficient to counteract the deleterious effect of CTLA4-Ig on Treg expansion and functionality, in keeping with the hypothesis that costimulatory blockade inhibits Treg expansion and function by limiting the delivery of essential CD28-dependent signals. Inhibition of regulatory T cell function should therefore be taken into account when designing tolerance protocols based on costimulatory blockade. Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons

The Big-5 and the perceived effectiveness of love acts

The present research was implemented in order to determine whether or not the Big-5 personality dimensions relate to the perceived effectiveness of love acts discovered in prior research. An internet based questionnaire was utilized and college undergraduates and as well as non-college students were included in the sample. The Big-5 dimensions of Agreeableness, Openness to Experience, and Emotional Stability were expected to be related to the perceived effectiveness of the Love acts. Additionally, men and women were expected to rate Love acts signaling commitment and exclusivity as most effective. The results obtained were consistent with the hypotheses and are discussed in terms of prior research.

Report from a consensus conference on antibody-mediated rejection in heart transplantation

The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation.

Self-Perceived Attractiveness and Its Influence on the Halo Effect and the Similar-to Me Effect

The present research examined the influences of the halo effect and the similar-tome effect on physical and sexual attractiveness for hiring decisions. It was hypothesized that the halo effect would cause applicants rated highly in physical and sexual attractiveness to receive higher ratings of hireability than unattractive applicants.However, if the similar-to-me effect is influential for levels of attractiveness in hiring situations, participants who rated themselves as less attractive should favor unattractive applicants. The results did not show an interaction between participant self-ratings and ratings of hireability, indicating the similar-to-me effect does not apply to physical or sexual attractiveness. There was a main effect of sexual attractiveness of the applicant forhireability, showing support for the halo effect. This effect was only found for White applicants, potentially due to in-group bias and out-group homogeneity.

Depressive symptoms, perceived social support, and prothrombotic measures in patients with venous thromboembolism

Psychosocial factors have been associated with both a prothrombotic state and an increased risk of venous thromboembolism (VTE). We examined the relation of depressive symptoms and social support with D-dimer, an integrative measure of enhanced coagulation activity, and several additional prothrombotic measures in patients with VTE.

1,25-Dihydroxycholecalciferol with low-calcium diet reduces acute rejection in rat lung allotransplantation

The effect of 1,25-dihydroxycholecalciferol (calcitriol, vitamin D3) with a low-calcium diet on the acute lung allograft rejection in a rat unilateral left lung transplantation model was evaluated.