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Transplant Tolerance: Current Insights and Strategies for Long-Term Survival of Xenografts

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Xenotransplantation is an attractive solution to the problem of allograft shortage. However, transplants across discordant species barriers are subject to vigorous immunologic and pathobiologic hurdles, some of which might be overcome with the induction of immunologic tolerance. Several strategies have been designed to induce tolerance to a xenograft at both the central (including induction of mixed chimerism and thymic transplantation) and peripheral (including adoptive transfer of regulatory cells and blocking T cell costimulation) levels. Currently, xenograft tolerance has been well-established in rodent models, but these protocols have not yet achieved similar success in nonhuman primates. This review will discuss the major barriers that impede the establishment of immunological tolerance across xenogeneic barriers and the potential solution to these challenges, and provide a perspective on the future of the development of novel tolerance-inducing strategies.

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Abbreviations

APCs:

Antigen-presenting cells

BMT:

Bone marrow transplantation

DCs:

Dendritic cells

GTKO:

Alpha 1,3-galactosyltransferase knockout

MAb:

Monoclonal antibody

MHC:

Major histocompatibility complex

MSCs:

Mesenchymal stem cells

SIRP-α:

Signal regulatory protein alpha

TCR:

T cell receptor

Tregs:

T regulatory cells

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Acknowledgements

This work was supported by National Key R&D Program of China (2017YFC1103704), National Natural Science Foundation of China (31500639), Shenzhen Foundation of Science and Technology (JCYJ20170307094549868, JCYJ20160427191926655, JCYJ20160427192552523, JCYJ20160229204849975 and GCZX2015043017281705), Fund for High Level Medical Discipline Construction of Shenzhen (2016031638), Sanming Project of Medicine in Shenzhen (SZSM201412020), Shenzhen Foundation of Health and Family Planning Commission (SZXJ2017021), Shenzhen Baoan District Science and Technology Bureau (2018JD124), Clinical Doctor-Basic Scientist Combination Foundation of Shenzhen Secondary people’s Hospital and Key Laboratory Project of Shenzhen Second People’s Hospital.

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Authors and Affiliations

  1. Shenzhen Xenotransplantation Medical Engineering Research and Development Center‚ Institute of Translational Medicine, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen University School of Medicine, Shenzhen University Health Science Center, Shenzhen, 518035, Guangdong, China

    Lu Liu, Hanchao Gao, Zhiming Cai & Lisha Mou

  2. Department of Gastroenterology‚ Center For Digestive Diseases, People’s Hospital of Baoan District, The 8th people’s Hospital of Shenzhen, Shenzhen, 518101, Guangdong, China

    Lu Liu, Jintao Liu, Zhiwu Lv & Ganlu Wang

  3. Department of Ophthalmology, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, Guangdong, China

    Chen He

  4. Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    Yifan Dai

  5. Xenotransplantation Program/Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, 35233, USA

    David K. C. Cooper

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  1. Lu Liu
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  2. Chen He
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  8. David K. C. Cooper
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  9. Zhiming Cai
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  10. Lisha Mou
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Correspondence to Lisha Mou.

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Liu, L., He, C., Liu, J. et al. Transplant Tolerance: Current Insights and Strategies for Long-Term Survival of Xenografts. Arch. Immunol. Ther. Exp. 66, 355–364 (2018). https://doi.org/10.1007/s00005-018-0517-7

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