Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo expanded regulatory T cells

Kenneth J. Scalapino, Qizhi Tang, Jeffrey A. Bluestone, Mark L. Bonyhadi, David I. Daikh

Research output: Contribution to journalArticlepeer-review

181 Scopus citations

Abstract

An increasing number of studies indicate that a subset of CD4+ T cells with regulatory capacity (regulatory T cells; Tregs) can function to control organ-specific autoimmune disease. To determine whether abnormalities of thymic-derived Tregs play a role in systemic lupus erythematosus, we evaluated Treg prevalence and function in (New Zealand Black × New Zealand White)F1 (BAV) lupus-prone mice. To explore the potential of Tregs to suppress disease, we evaluated the effect of adoptive transfer of purified, ex vivo expanded thymic-derived T regs on the progression of renal disease. We found that although the prevalence of Tregs is reduced in regional lymph nodes and spleen of prediseased B/W mice compared with age-matched non-autoimmune mice, these cells increase in number in older diseased mice. In addition, the ability of these cells to proliferate in vitro was comparable to those purified from non-autoimmune control animals. Purified CD4+CD25 +CD62Lhigh B/W Tregs were expanded ex vivo 80-fold, resulting in cells with a stable suppressor phenotype. Adoptive transfer of these exogenously expanded cells reduced the rate at which mice developed renal disease; a second transfer after treated animals had developed proteinuria further slowed the progression of renal disease and significantly improved survival. These studies indicate that thymic-derived Tregs may have a significant role in the control of autoimmunity in lupus-prone B/W mice, and augmentation of these cells may constitute a novel therapeutic approach for systemic lupus erythematosus.

Original languageEnglish (US)
Pages (from-to)1451-1459
Number of pages9
JournalJournal of Immunology
Volume177
Issue number3
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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