Natural CD8+CD122+ T cells are more potent in suppression of allograft rejection than CD4+CD25+ regulatory T cells

Z. Dai, S. Zhang, Q. Xie, S. Wu, J. Su, S. Li, Y. Xu, X. C. Li

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Despite extensive studies on CD4+CD25+ regulatory T cells (Tregs), their application in adoptive transfer therapies is still not optimal in immune-competent wild-type (WT) animal models. Therefore, it is compelling to search for more potent Tregs for potential clinical application. Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are also Tregs. However, their suppression in allograft rejection, efficiency in suppression and underlying mechanisms remain unclear. Using a murine allotransplantation model, we reported here that CD8+CD122+ Tregs were actually more potent in suppression of allograft rejection and underwent more rapid homeostatic proliferation than their CD4+CD25+ counterparts. Moreover, they produced more IL-10 and were more potent in suppressing T cell proliferation in vitro. Deficiency in IL-10 in CD4+CD25+ and CD8+CD122+ Tregs resulted in their reduced but equal suppression in vivo and in vitro, suggesting that IL-10 is responsible for more effective suppression by CD8+CD122+ than CD4+CD25+ Tregs. Importantly, transfer of CD8+CD122+ Tregs together with the administration of recombinant IL-15 significantly prolonged allograft survival in WT mice. Thus, for the first time, we demonstrate that naturally arising CD8+CD122+ Tregs not only inhibit allograft rejection but also exert this suppression more potently than their CD4+CD25+ counterparts. This novel finding may have important implications for tolerance induction. In search of more efficient subsets of regulatory T cells, the authors find that naturally arising CD8+CD122+ T cells are more potent suppressors of allograft rejection than conventional CD4+CD25+ regulatory T cells. See editorial by Lerret and Luo on page 7.

Original languageEnglish (US)
Pages (from-to)39-48
Number of pages10
JournalAmerican Journal of Transplantation
Volume14
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • Allograft rejection
  • T cell
  • Treg

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

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