Foxp3-deficient regulatory T cells do not revert into conventional effector CD4+ T cells but constitute a unique cell subset

Michal Kuczma, Robert Podolsky, Nikhil Garge, Danielle Daniely, Rafal W Pacholczyk, Leszek Ignatowicz, Piotr Kraj

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Homeostasis in the immune system is maintained by specialized regulatory CD4+ T cells (Treg) expressing transcription factor Foxp3. According to the current paradigm, high-affinity interactions between TCRs and class II MHC-peptide complexes in thymus "instruct" developing thymocytes to up-regulate Foxp3 and become Treg cells. However, the loss or down-regulation of Foxp3 does not disrupt the development of T reg cells but abrogates their suppressor function. In this study, we show that Foxp3-deficient Treg cells in scurfy mice harboring a null mutation of the Foxp3 gene retained cellular features of Treg cells including in vitro anergy, impaired production of inflammatory cytokines, and dependence on exogenous IL-2 for proliferation and homeostatic expansion. Foxp3-deficient Treg cells expressed a low level of activation markers, did not expand relative to other CD4+ T cells, and produced IL-4 and immunomodulatory cytokines IL-10 and TGF-β when stimulated. Global gene expression profiling revealed significant similarities between T reg cells expressing and lacking Foxp3. These results argue that Foxp3 deficiency alone does not convert Treg cells into conventional effector CD4+ T cells but rather these cells constitute a distinct cell subset with unique features.

Original languageEnglish (US)
Pages (from-to)3731-3741
Number of pages11
JournalJournal of Immunology
Volume183
Issue number6
DOIs
StatePublished - Sep 15 2009

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ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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