Primed macrophages directly and specifically reject allografts

Abstract

Monocytes and macrophages have long been associated with acute and chronic allograft rejection; this is mediated by their abilities to promote inflammation, kill target cells via antibody-dependent cytotoxicity and modulate adaptive immunity. Our present study showed that allogeneic antigen-primed macrophages acutely rejected skin grafts with specificity after adoptive transfer into MHC-matched immunodeficient mice. The ability of primed macrophages to reject allografts essentially requires the help of CD4+ T cells and does not require the help of CD8+ T cells. Moreover, the primed, perforin-deficient macrophages rejected the skin grafts in a significantly delayed pattern compared with WT macrophages, indicating that the perforin pathway of the primed macrophages is likely involved in the rejection process. Thus, primed macrophages are endowed with adaptive immunity-like features, such as specificity, with the help of CD4+ T cells during the immune response to allografts. The present study challenges our traditional views of macrophage functions and highlights the biological functions of macrophages beyond innate immunity in mammals.

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Acknowledgements

We wish to thank Dr. Zhanfeng Liang for his kind editing of the manuscript, Mrs. Qing Meng for her expert technical assistance, Mrs. Ling Li for her excellent laboratory management, and Mr. Baisheng Ren for his outstanding animal husbandry. This work was supported by grants from the National Key R&D Program of China (2017YFA0105002 and 2017YFA0104402 to Y.Z.), the National Science and Technology Major Project (2017ZX10201101), the National Natural Science Foundation for General and Key Programs (C81530049 and U1738111 to Y.Z.), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030301 and XDA04020202-19 to Y.Z.), and the China Manned Space Flight Technology Project (TZ-1, Y.Z.).

Author information

Z.C. designed and performed the adoptive transfer studies and analyzed the data; C.S. designed and performed the experiments with the cells and mice and analyzed the data; L.S. performed the real-time PCR assays and the molecular studies and analyzed the data; C.F. performed the immunostaining assays and flow cytometry assays; F.Y. designed and performed the ex vivo studies and analyzed the data; Y.X. performed histology assays; and Y.Z. provided overall supervision, designed the experiments, analyzed the data, and wrote the manuscript.

Correspondence to Yong Zhao.

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The authors declare no competing interests.

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Chu, Z., Sun, C., Sun, L. et al. Primed macrophages directly and specifically reject allografts. Cell Mol Immunol (2019) doi:10.1038/s41423-019-0226-0

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Key words

  • Macrophages
  • Specificity
  • Graft rejection
  • Innate immunity
  • Transplantation

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