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

29 Citations (Scopus)

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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Regulatory T-Lymphocytes
T-Lymphocytes
Cytokines
Gene Expression Profiling
Thymocytes
Interleukin-4
Interleukin-10
Thymus Gland
Interleukin-2
Immune System
Homeostasis
Transcription Factors
Up-Regulation
Down-Regulation
Peptides
Mutation
Genes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Foxp3-deficient regulatory T cells do not revert into conventional effector CD4+ T cells but constitute a unique cell subset. / Kuczma, Michal; Podolsky, Robert; Garge, Nikhil; Daniely, Danielle; Pacholczyk, Rafal W; Ignatowicz, Leszek; Kraj, Piotr.

In: Journal of Immunology, Vol. 183, No. 6, 15.09.2009, p. 3731-3741.

Research output: Contribution to journalArticle

Kuczma, Michal ; Podolsky, Robert ; Garge, Nikhil ; Daniely, Danielle ; Pacholczyk, Rafal W ; Ignatowicz, Leszek ; Kraj, Piotr. / Foxp3-deficient regulatory T cells do not revert into conventional effector CD4+ T cells but constitute a unique cell subset. In: Journal of Immunology. 2009 ; Vol. 183, No. 6. pp. 3731-3741.
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