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Trichomonosis is an endemic disease in cattle that are reared under extensive conditions and bred by natural mating. It causes profound economic losses to the producers by increasing calving interval, increasing embryo losses, and decreasing pregnancy rates. The aim of this study was to determine whether Tritrichomonas foetus infections were absent from cattle in St. Kitts. Using the modified hypergeometric method, preputial samples from bulls (n = 78) were tested using the InPouch™ culture for presence of T. foetus. Results highlighted an absence of trichomoniasis in bulls on St. Kitts with a 95% confidence.

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Though islet transplantation has emerged as a promising therapeutic for type 1 diabetes, the immunosuppressive agents that prevent rejection carry significant risk of morbidity. Adoptive transfer of chimeric antigen receptor (CAR) Tregs has the potential to protect allografts and transform transplantation medicine in the way that CAR T cells have revolutionized the treatment of cancer. However, there lacks a large animal model in which to optimize the safety and efficacy of CAR Treg therapy. Therefore, we developed methods to sort, transduce, and expand Cynomolgus macaque CAR Tregs recognizing the human/non-human primate cross-reactive alloantigen Bw6. Our novel pan-primate artificial antigen presenting cells expanded Tregs to clinical sized doses of >500 million cells from as few as 25k sorted cells. Expanded Tregs expressed protein and epigenetic markers indicative of stable CAR Tregs and displayed suppressor function without cytotoxicity. CAR Tregs transferred into an antigen negative recipient could be detected for 7 days in peripheral blood and 1 month in bone marrow. When transferred to a diabetic recipient simultaneously with allogeneic Bw6+ islets, islets were partially protected from rejection as measured by increased control of blood glucose with insulin treatment. Transferred Tregs persisted in peripheral blood for >34 days while displaying markers of stable, activated Tregs including CAR, FoxP3, and Helios. Importantly, we could not detect CAR+ FoxP3− effector T cells which would target the graft and expedite graft rejection. Our results provide a proof of concept for CAR Treg adoptive therapy in a large animal model and establish a framework for optimization of therapy before a clinical trial in humans.

No abstract