Frontiers in Immunology (Jun 2018)

Human CD8+CD28− T Suppressor Cells Expanded by IL-15 In Vitro Suppress in an Allospecific and Programmed Cell Death Protein 1-Dependent Manner

  • Fu Feng,
  • Yanjun Liu,
  • Guihuan Liu,
  • Ping Zhu,
  • Manman Zhu,
  • Hua Zhang,
  • Xiao Lu,
  • Jiumin Liu,
  • Xunrong Luo,
  • Yuming Yu

DOI
https://doi.org/10.3389/fimmu.2018.01442
Journal volume & issue
Vol. 9

Abstract

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CD8+CD28− T suppressor cells (Ts) have been recently documented to play an important role in alloimmunity. Therefore, understanding and optimizing the conditions under which these cells are generated and/or expanded would greatly facilitate further research and potential clinical use. In this study, we describe rapid expansion of human allospecific CD8+CD28− Ts cells through coculture of CD8+ T cells with human leukocyte antigen-mismatched donor antigen-presenting cells plus IL-15 in a relative short period of time in vitro. Interestingly, IL-15 promotes the expansion of CD8+CD28− Ts cells through several parallel mechanisms. The expanded CD8+CD28− Ts cells upregulate expression of CD132, CD25, and programmed cell death protein 1 (PD-1), but downregulate expression of CD122, GZM-B, and perforin, while exhibiting no cytotoxicity. Most importantly, the expanded CD8+CD28− Ts cells vigorously inhibit CD4+ T cells proliferation in a contact-dependent and donor-specific manner both in vitro and in vivo. Interestingly, the co-inhibitory molecules PD-1 and programmed death-ligand 1 play an obligatory role in the mechanisms of CD8+CD28− Ts cells suppression. Taken together, our study report novel methodology for IL-15-induced expansion of human CD8+CD28− Ts cells and possible mechanisms. These findings may facilitate understanding of transplant rejection and promote clinical application of CD8+CD28− Ts cell-based strategies for inducing and monitoring transplant tolerance in the future.

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