title: Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells.
abstract: Foxp3 plays a key role in CD4+ CD25+ T(reg) cell function in mice and represents a specific marker for these cells. Despite the strong association between FOXP3 expression and regulatory function in fresh human T cells, little is known about the dynamics of endogenous FOXP3 expression and its relation to the suppressive function in activated human T cells. Here, we addressed the dynamics of FOXP3 expression during human CD4+ T cell activation by plate-bound anti-CD3 Ab as well as the relationship between its expression and regulatory function at the single-cell level. Our data show that FOXP3 is expressed in a high percentage of activated T cells after in vitro stimulation of human CD4+ CD25- cells. FOXP3 expression is strongly associated with hyporesponsiveness of activated T cells, but is not directly correlated with their suppressive capabilities, as we demonstrate that it is also expressed in activated nonsuppressive T cells. However, in this nonsuppressive T cell population, FOXP3 expression is transient, while it is stably expressed in activated T cells that do display suppressive function, and in natural CD4+ CD25++ T(reg) cells. These data indicate that expression of endogenous FOXP3, in humans, is not sufficient to induce regulatory T cell activity or to identify T(reg) cells.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Andreea
authors.initials: A
authors.lastname: Ioan-Facsinay
authors.forename: Ellen I H
authors.initials: EI
authors.lastname: van der Voort
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D013997:Time Factors
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit