CD4+ and CD8+ Regulatory T Cells Generated Ex Vivo with IL-2 and TGF-β Suppress a Stimulatory Graft-versus-Host Disease with a Lupus-Like Syndrome

Song Guo Zheng, Ju Hua Wang, Michael N. Koss, Francisco Quismorio, J. Dixon Gray, David Allen Horwitz

Research output: Contribution to journalArticlepeer-review

191 Scopus citations

Abstract

Regulatory T cells generated ex vivo from conventional mouse T cells have been used to prevent and alter the course of a stimulatory graft-vs-host disease with a lupus-like syndrome. DBA/2 mouse T cells induce this syndrome when injected into (DBA/2 × C57BL/6) F1 mice. Stimulating DBA/ 2 T cells with irradiated C57BL/6 in the presence of IL-2 and TGF-β induced both CD4+ and CD8+ cells to develop potent suppressive activity and enhanced their survival. The IL-2 and TGF-β-treated T cells lost their ability to induce graft-vs-host disease and, instead, prevented other parental T cells from inducing lymphoid hyperplasia, B cell activation, and an immune complex glomerulonephritis. Moreover, a single transfer of TGF-β-conditioned T cells to animals that had already developed anti-dsDNA Abs decreased the titer, suppressed proteinuria, and doubled survival. This study raises the possibility that autologous regulatory T cells generated ex vivo have the potential to be used as an adoptive immunotherapy to induce allograft tolerance and to control autoimmunity.

Original languageEnglish (US)
Pages (from-to)1531-1539
Number of pages9
JournalJournal of Immunology
Volume172
Issue number3
DOIs
StatePublished - Feb 1 2004

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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