Intragraft regulatory T cells in the modern era: what can high-dimensional methods tell us about pathways to allograft acceptance?

Replacement of diseased organs with transplanted healthy donor ones remains the best and often only treatment option for end-stage organ disease. Immunosuppressants have decreased the incidence of acute rejection, but long-term survival remains limited. The broad action of current immunosuppressive drugs results in global immune impairment, increasing the risk of cancer and infections. Hence, achievement of allograft tolerance, in which graft function is maintained in the absence of global immunosuppression, has long been the aim of transplant clinicians and scientists. Regulatory T cells (Treg) are a specialized subset of immune cells that control a diverse array of immune responses, can prevent allograft rejection in animals, and have recently been explored in early phase clinical trials as an adoptive cellular therapy in transplant recipients. It has been established that allograft residency by Tregs can promote graft acceptance, but whether intragraft Treg functional diversification and spatial organization contribute to this process is largely unknown. In this review, we will explore what is known regarding the properties of intragraft Tregs during allograft acceptance and rejection. We will summarize recent advances in understanding Treg tissue residency through spatial, transcriptomic and high-dimensional cytometric methods in both animal and human studies. Our discussion will explore properties of intragraft Tregs in mediating operational tolerance to commonly transplanted solid organs. Finally, given recent developments in Treg cellular therapy, we will review emerging knowledge of whether and how these adoptively transferred cells enter allografts in humans. An understanding of the properties of intragraft Tregs will help lay the foundation for future therapies that will promote immune tolerance.

[Greenhouse gas emissions, carbon leakage and net carbon sequestration from afforestation and forest management: A review.] / æ£®æž—ç»è¥ä¸Žç®¡ç†ä¸‹çš„æ¸©å®¤æ°”ä½“æŽ’æ”¾ã€ç¢³æ³„æ¼å’Œå‡€å›ºç¢³é‡ç ”ç©¶è¿›å±•.

Forests play an important role in climate change mitigation and concentration of CO2 reduction in the atmosphere. Forest management, especially afforestation and forest protection, could increase carbon stock of forests significantly. Carbon sequestration rate of afforestation ranges from 0.04 to 7.52 t C·hm-2·a-1, while that of forest protection is 0.33-5.20 t C·hm-2·a-1. At the same time, greenhouse gas (GHG) is generated within management boundary due to the production and transportation of the materials consumed in relevant activities of afforestation and forest management. In addition, carbon leakage is also generated outside boundary from activity shifting, market effects and change of environments induced by forest management. In this review, we summarized the definition of emission sources of GHG, monitoring methods, quantity and rate of greenhouse gas emissions within boundary of afforestation and forest management. In addition, types, monitoring methods and quantity of carbon leakage outside boundary of forest management were also analyzed. Based on the reviewed results of carbon sequestration, we introduced greenhouse gas emissions within boundary and carbon leakage, net carbon sequestration as well as the countervailing effects of greenhouse gas emissions and carbon leakage to carbon sequestration. Greenhouse gas emissions within management boundary counteract 0.01%-19.3% of carbon sequestration, and such counteraction could increase to as high as 95% considering carbon leakage. Afforestation and forest management have substantial net carbon sequestration benefits, when only taking direct greenhouse gas emissions within boundary and measurable carbon leakage from activity shifting into consideration. Compared with soil carbon sequestration measures in croplands, afforestation and forest management is more advantageous in net carbon sequestration and has better prospects for application in terms of net mitigation potential. Along with the implementation of the new stage of key ecological stewardship projects in China as well as the concern on carbon benefits brought by projects, it is necessary to make efforts to increase net carbon sequestration via reducing greenhouse gas emissions and carbon leakage. Rational planning before start-up of the projects should be promoted to avoid carbon emissions due to unnecessary consumption of materials and energy. Additionally, strengthening the control and monitoring on greenhouse gas emissions and carbon leakage during the implementation of projects are also advocated.

[Greenhouse gas emissions and net carbon sequestration of "Grain for Green" Program in China.] / 中国退耕还林工程温室气体排放与净固碳量.

Based on the estimation of carbon cost from afforestation in project boundary and carbon leakage out of boundary in the construction period of "Grain for Green" Program (GGP) (2000-2010), the annual variance and composition of the carbon cost and carbon leakage, as well as characters of variance of net carbon sequestration were analyzed for GGP and respective program regions. Results showed that the carbon costs in northwest region, southwest region, northeast region, north region and central south and east region were 3.38, 3.64, 1.03, 1.66 and 4.38 Tg C, respectively, totaling 14.09 Tg C. Meanwhile the carbon leakages of the above regions were 21.33, 4.60, 5.50, 1.32 and 3.78 Tg C, respectively, and 36.53 Tg C in total. The composition characters of the carbon costs of the GGP and the respective regions were similar. Carbon emissions from afforestation were the largest carbon cost, and afforestation on converted farmland was the main carbon emission source. Accordingly, among the materials consumed, fertilizer brought about the largest carbon cost, followed by building materials, while carbon emissions from fuels, irrigation, herbicides and pesticides only accounted for about 10% for respective regions. The carbon cost and carbon leakage of the GGP were 50.62 Tg C in total, which counteracted 19.9% of the sequestered carbon in the program. In northwest region, southwest region, northeast region, north region and central south and east region, carbon emissions (including cost and leakage) accounted for 38.9%, 10.4%, 26.1%, 8.9% and 15.5% of the carbon sequestration, respectively. The net carbon sequestration of the GGP was 203.50 Tg C with an annual average of 18.50 Tg C·a-1. The carbon cost and leakage offset a minor part of the carbon sequestration of the GGP. Therefore, the GGP contributed significantly to greenhouse gas mitigation in China as well as global climate warming mitigation. Adopting precision fertilization in economic forest afforestation and supplying alternative livelihoods to farmers in the program could be the potential measures to reduce carbon cost and carbon leakage.