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Approaches that prevent acute rejection of renal transplants in a rhesus monkey model were studied to determine a common mechanism of acceptance. After withdrawal of immunosuppression, all 14 monkeys retained normal allograft function for >6 mo. Of these, nine rejected their renal allograft during the study, and five maintained normal function throughout the study period. The appearance of TGF-β1+ interstitial mononuclear cells in the graft coincided with a nonrejection histology, whereas the absence/disappearance of these cells was observed with the onset of rejection. Analysis with a variety of TGF-β1-reactive Abs indicated that the tolerance-associated infiltrates expressed the large latent complex form of TGF-β1. Peripheral leukocytes from rejecting monkeys lacking TGF-β1+ allograft infiltrates responded strongly to donor Ags in delayed-type hypersensitivity trans-vivo assays. In contrast, allograft acceptors with TGF-β1+ infiltrates demonstrated a much weaker peripheral delayed-type hypersensitivity response to donor alloantigens (p < 0.01 vs rejectors), which could be restored by Abs that either neutralized active TGF-β1 or blocked its conversion from latent to active form. Anti-IL-10 Abs had no restorative effect. Accepted allografts had CD8+ and CD4+ interstitial T cell infiltrates, but only the CD4+ subset included cells costaining for TGF-β1. Our data support the hypothesis that the recruitment of CD4+ T regulatory cells to the allograft interstitium is a final common pathway for metastable renal transplant tolerance in a non-human primate model.

ABI793 induces prolonged renal allograft survival in rhesus monkeys. Nevertheless, thromboembolic complications may occur and chronic allograft nephropathy may develop after anti-CD154 treatment is discontinued.

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ABSTRACT. We report a cervical intraspinal cyst in a dog that was initially tetraparetic but spontaneously recovered completely. MRI revealed a well-demarcated intraspinal cyst located dorsally to a degenerated intervertebral disc. The location of the cyst and its signal features on MRI resembled those of discal cysts previously reported in humans. It has been reported in dogs that clinical signs of a intraspinal cyst are similar to those of intervertebral disc herniation and both conditions require surgical intervention. Unexpectedly, our case showed rapid spontaneous recovery and the follow-up MRI revealed complete resolution of the intraspinal cyst and spinal cord compression. Spontaneous recovery of degenerative intraspinal cyst may occur in dogs, similar to rare human cases as reported previously.KEY WORDS: canine, intervertebral disc disease, intraspinal cyst, magnetic resonance imaging.

ABSTRACT. Canine degenerative myelopathy is an adult-onset, progressive neurodegenerative disease that occurs in multiple dog breeds, particularly Pembroke Welsh Corgis. Recently, a degenerative myelopathy-associated mutation of the canine SOD1 gene was identified as c.118G>A (p.E40K). In the present study, genotyping assays using conventional and real-time PCR methods were developed, and a preliminary genotyping survey was performed on 122 randomly selected Pembroke Welsh Corgis without any degenerative myelopathy-related clinical signs to determine the current allele frequency in Japan. Both of the assays provided clear-cut genotyping. The survey demonstrated the frequencies of the G/G wild-type, G/A heterozygote and A/A homozygote to be 9.0, 42.6 and 48.4%, respectively, indicating that the prevalence of the mutant A allele (69.7%) in Pembroke Welsh Corgis is extremely high in Japan.