Expression of CTLA-4 and FOXP3 in cis protects from lethal lymphoproliferative disease

Shunsuke Chikuma, Jeffrey A. Bluestone

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


Both CTLA-4-deficient and FoxP3-deficient mice exhibit a short life span due to massive lymphoproliferation (LP) and a systemic autoimmune-like syndrome. Although it has been postulated that both diseases result from regulatory T cell (Treg) defects, there have been no direct complementation studies to elucidate their relationship in homeostatic lymphocyte proliferation during the neonatal period. In this study, reconstitution of sublethally irradiated RAG KO mice with either CTLA-4-deficient or FoxP3-deficient bone marrow (BM) resulted in LP disease similar to that observed in CTLA-4 KO or Scurfy mice, respectively. Although co-injection of BM from wild-type mice inhibited the activation of CTLA-4-deficient or FoxP3-deficient T cells and ameliorated LP disease through extrinsic regulatory mechanisms by Treg cells, mice that had received the BM mixture of Scurfy and CTLA-4 KO BM eventually died of incomplete protection. These results suggest common attributes of both diseases, but expression of both CTLA-4 and FoxP3 on the same cell subset is essential to fully prevent LP disease.

Original languageEnglish
Pages (from-to)1285-1289
Number of pages5
JournalEuropean Journal of Immunology
Issue number5
Publication statusPublished - 2007 May
Externally publishedYes


  • Autoimmunity
  • Costimulation
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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