Effective expansion of alloantigen-specific Foxp3+ CD25 + CD4+ regulatory T cells by dendritic cells during the mixed leukocyte reaction Academic Article uri icon

Overview

MeSH Major

  • Antigens, CD4
  • Dendritic Cells
  • Forkhead Transcription Factors
  • Isoantigens
  • Receptors, Interleukin-2
  • T-Lymphocytes, Regulatory

abstract

  • Thymic-derived CD25+ CD4+ T regulatory cells (Tregs) suppress immune responses, including transplantation. Here we evaluated the ability of dendritic cells (DCs) to expand alloantigen-specific Tregs in the mixed leukocyte reaction (MLR) that develops from polyclonal populations of T cells. The allogeneic DCs, when supplemented with IL-2 in the cultures, were much more effective than bulk spleen cells in expanding the numbers of Tregs. Likewise, DCs and not spleen cells were effective in sustaining expression of the transcription factor Foxp3 in Tregs, but neither IL-2 nor CD80/86 was required for this effect in the cultures. On a per-cell basis, the DC-expanded, but not unexpanded, Tregs were more potent suppressors of a fresh MLR by CD25- CD4+ T cells. Suppression was 3- to 10-fold more active for MLRs induced by the original alloantigens than for third-party stimulators. When DC-expanded Tregs were introduced into sublethally irradiated hosts, the T cells suppressed graft-versus-host-disease induced by CD25- CD4+ T cells. Again, suppression was more active against the same mouse strain that provided the DCs to expand the Tregs. Therefore, alloantigen-selected Tregs are more effective suppressors of responses to major transplantation antigens, and these Tregs can be expanded from a polyclonal repertoire by DCs.

publication date

  • February 21, 2006

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1413800

Digital Object Identifier (DOI)

  • 10.1073/pnas.0510606103

PubMed ID

  • 16473944

Additional Document Info

start page

  • 2758

end page

  • 63

volume

  • 103

number

  • 8