Is FOXP3 a bona fide marker for human regulatory T cells?

FOXP3 is a specific marker for naturally occurring regulatory T cells (nTreg). FOXP3 expression is correlated with development and function of nTreg. Recent evidence suggests that, upon activation, human effector T (Teff) cells and type 1 regulatory T (Tr1) cells can express FOXP3, albeit transiently. While the role of transient FOXP3 expression in Teff cells is poorly understood, it is becoming clear that it does not correlate with suppressor function. Furthermore, FOXP3‐independent mechanisms, mediated by IL‐10, contribute to the induction and suppressor functions of Tr1 cells.

[1]  Edgar Schmitt,et al.  Epigenetic Control of the foxp3 Locus in Regulatory T Cells , 2007, PLoS biology.

[2]  A. Scheffold,et al.  Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL‐)two to tango , 2005, European journal of immunology.

[3]  T. Nomura,et al.  Control of Regulatory T Cell Development by the Transcription Factor Foxp3 , 2002 .

[4]  Vincent C. Manganiello,et al.  Foxp3-dependent programme of regulatory T-cell differentiation , 2007, Nature.

[5]  Peter R. Galle,et al.  Cutting Edge: TGF-β Induces a Regulatory Phenotype in CD4+CD25− T Cells through Foxp3 Induction and Down-Regulation of Smad7 , 2004, The Journal of Immunology.

[6]  F. Ramsdell,et al.  An essential role for Scurfin in CD4+CD25+ T regulatory cells , 2003, Nature Immunology.

[7]  H. Ochs,et al.  Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis , 2003, Current opinion in rheumatology.

[8]  F. Powrie,et al.  Characterization of Foxp3+CD4+CD25+ and IL-10-Secreting CD4+CD25+ T Cells during Cure of Colitis1 , 2006, The Journal of Immunology.

[9]  C. Karagiannidis,et al.  Molecular Mechanisms Underlying FOXP3 Induction in Human T Cells1 , 2006, The Journal of Immunology.

[10]  Yang Liu,et al.  FOXP3 is a novel transcriptional repressor for the breast cancer oncogene SKP2. , 2007, The Journal of clinical investigation.

[11]  S. Ziegler,et al.  De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25- cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Hervé Groux,et al.  A CD4+T-cell subset inhibits antigen-specific T-cell responses and prevents colitis , 1997, Nature.

[13]  Fiona Powrie,et al.  Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single‐cell level , 2005, European journal of immunology.

[14]  E. Shevach,et al.  Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype. , 2007, Blood.

[15]  P. Lipsky,et al.  Deficient CD4+CD25high T Regulatory Cell Function in Patients with Active Systemic Lupus Erythematosus1 , 2007, The Journal of Immunology.

[16]  S. Ziegler,et al.  The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs. , 2005, The Journal of clinical investigation.

[17]  M. Roncarolo,et al.  Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. , 2005, Blood.

[18]  T. Huizinga,et al.  Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells , 2007, European journal of immunology.

[19]  Shimon Sakaguchi,et al.  Foxp3: a critical regulator of the development and function of regulatory T cells. , 2004, Microbes and infection.

[20]  A. Rudensky,et al.  Regulatory T cell lineage specification by the forkhead transcription factor foxp3. , 2005, Immunity.

[21]  L. Naldini,et al.  Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

[22]  T. Nomura,et al.  Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. , 2004, International immunology.

[23]  L. Goldsmith,et al.  Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. , 2004, Archives of dermatology.

[24]  B. Stockinger,et al.  IL-10-Secreting Regulatory T Cells Do Not Express Foxp3 but Have Comparable Regulatory Function to Naturally Occurring CD4+CD25+ Regulatory T Cells 1 , 2004, The Journal of Immunology.

[25]  S. Ziegler,et al.  Defective regulatory and effector T cell functions in patients with FOXP3 mutations. , 2006, The Journal of clinical investigation.

[26]  M. Roncarolo,et al.  Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. , 2007, International immunology.

[27]  J. Buer,et al.  Inhibition of the Transcription Factor Foxp3 Converts Desmoglein 3-Specific Type 1 Regulatory T Cells into Th2-Like Cells1 , 2006, The Journal of Immunology.

[28]  S. Ziegler FOXP3: of mice and men. , 2006, Annual review of immunology.

[29]  A. Rudensky,et al.  Foxp3 programs the development and function of CD4+CD25+ regulatory T cells , 2003, Nature Immunology.

[30]  E. Bonifacio,et al.  Induction of Tolerance in Type 1 Diabetes via Both CD4+CD25+ T Regulatory Cells and T Regulatory Type 1 Cells , 2006, Diabetes.

[31]  Christophe Benoist,et al.  Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. , 2007, Immunity.

[32]  S. Ziegler,et al.  Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. , 2003, The Journal of clinical investigation.