Alloreactive memory T cells are present in virtually all transplant recipients due to prior sensitization or heterologous immunity and mediate injury undermining graft outcome. In mouse models, endogenous memory CD8 T cells infiltrate MHC-mismatched cardiac allografts and produce IFN-γ in response to donor class I MHC within 24 hours post-transplant. The current studies analyzed the efficacy of anti-LFA-1 mAb to inhibit early CD8 T cell cardiac allograft infiltration and activation. Anti-LFA-1 mAb given to C57BL/6 6 (H-2b) recipients of A/J (H-2a) heart grafts on days −1 and 0 completely inhibited CD8 T cell allograft infiltration, markedly decreased neutrophil infiltration, and significantly reduced intra-graft expression levels of IFN-γ-induced genes. Donor-specific T cells producing IFN-γ were at low/undetectable numbers in spleens of anti-LFA-1 mAb treated recipients until day 21. These effects combined to promote substantial prolongation (from day 8 to 27) in allograft survival. Delaying anti-LFA-1 mAb treatment until days 3 and 4 post-transplant did not inhibit early memory CD8 T cell infiltration and proliferation within the allograft. These data indicate that peri-transplant anti-LFA-1 mAb inhibits early donor-reactive memory CD8 T cell allograft infiltration and inflammation suggesting an effective strategy to attenuate the negative effects of heterologous immunity in transplant recipients.
The integration of multiple sensory modalities allows us to adapt to the environment of the outside world. It is widely known that visual stimuli interfere with the processing of auditory information, which is involved in the ability to pay attention. Additionally, visuospatial attention has the characteristic of laterality. It is unclear whether this laterality of visuospatial attention affects the processing of auditory stimuli. The sensorimotor gating system is a neurological process, which filters out unnecessary stimuli from environmental stimuli in the brain. Prepulse inhibition (PPI) is an operational measure of the sensorimotor gating system, which a weaker prestimulus (prepulse), such as a visual stimulus, inhibits the startle reflex elicited by a subsequent robust startling stimulus (pulse) such as a tone. Therefore, we investigated whether the visual stimulus from the left or right visual space affects the sensorimotor gating system in a “rest” task (low attentional condition) and a “selective attention” task (high attentional condition). In the selective attention task, we found that the target prepulse presented in the left and bilateral visual fields suppressed the startle reflex more than that presented in the right visual field. By contrast, there was no laterality of PPI in the no-target prepulse condition, and there was no laterality of PPI in the rest task. These results suggest that the laterality of visuospatial attention affects the sensorimotor gating system depending on the attentional condition. Moreover, the process of visual information processing may differ between the left and right brain.
Purpose. To retrospectively evaluate the clinical significance of radiotherapy for oligometastases of bone in prostate cancer (PCa). Methods and Materials. Between 2003 and 2008, 35 PCa patients with oligometastases of bone were treated with radiotherapy. Results. The median radiotherapy dose was 40 Gy. The 3-year overall survival rates for all patients, for patients that received a radiotherapy dose of ≥40 Gy (n = 21) and for those that received <40 Gy (n = 14), were 77.2%, 90.5%, and 50.0%, respectively. Fourteen out of 16 patients (87.5%) who had pain were improved 1 month after radiotherapy. The median duration of pain relief was 12 months. Pathological fracture and spinal cord compression (SCC) were not seen at the treated sites but developed at nonirradiated sites in three patients (8.6%) and in one patient (2.8%), respectively. Although the high-dose group (≥40 Gy) achieved better survival than the low-dose group (<40 Gy), it was not independent prognostic factor in multivariable analysis. Conclusions. Radiotherapy of bone oligometastases in PCa was effective for long-term pain relief. Pathological fracture and SCC were not seen at the treated sites. A larger clinical trial is warranted to study the actual benefit following radiotherapy for oligometastases of bone in PCa.
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