Donor lymphocyte infusion induces long-term donor-specific cardiac xenograft survival through activation of recipient double-negative regulatory T cells

Wenhao Chen, Dejun Zhou, Jose R. Torrealba, Thomas K. Waddell, David Grant, Li Zhang

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Previous studies have shown that pretransplant donor lymphocyte infusion (DLI) can enhance xenograft survival. However, the mechanism by which DLI induces xenograft survival remains obscure. Using T cell subset-deficient mice as recipients we show that CD4+, but not CD8+, T cells are necessary to mediate the rejection of concordant cardiac xenografts. Adoptive transfer of naive CD4+ T cells induces rejection of accepted cardiac xenografts in CD4-/- mice. This rejection can be prevented by pretransplant DLI in the absence of any other treatment. Furthermore, we demonstrate that DLI activates αβ-TCR+CD3 +CD4-CD8- double-negative (DN) regulatory T (Treg) cells in xenograft recipients, and that DLI-activated DN Treg cells can inhibit the proliferation of donor-specific xenoreactive CD4+ T cells in vitro. More importantly, adoptive transfer of DLI-activated DN Treg cells from xenograft recipients can suppress the proliferation of xenoreactive CD4+ T cells and their ability to produce IL-2 and IFN-γ in vivo. Adoptive transfer of DLI-activated DN Treg cells also prevents CD4 + T cell-mediated cardiac xenograft rejection in an Ag-specific fashion. These data provide direct evidence that DLI can activate recipient DN Treg cells, which can induce donor-specific long-term cardiac xenograft survival by suppressing the proliferation and function of donor-specific CD4+ T cells in vivo.

Original languageEnglish (US)
Pages (from-to)3409-3416
Number of pages8
JournalJournal of Immunology
Volume175
Issue number5
DOIs
StatePublished - Sep 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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