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

Abstract

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. See accompanying commentary:

Prednisolone Treatment Induces Tolerogenic Dendritic Cells and a Regulatory Milieu in Myasthenia Gravis Patients

“…Phenotypically, they are diverse in terms of FOXP3 expression, and in the cytokines that they produce, probably depending on the conditions that induce their differentiation. In addition, it is now known that FOXP3 can be expressed transiently in non-Treg cells upon activation, suggesting that this molecule may harbor a more diverse set of functions as assumed originally (56,57). In our experiments, the expression of FOXP3 was comparable in all three CD4 ϩ T cell lines after stimulation with differentially generated DCs (data not shown).…”

Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer

“…One possible explanation is the fact that although FoxP3 is currently the best marker available for immunohistochemical staining of Treg on paraYn embedded tissue, it is not exclusively expressed in regulatory cells. Recently, it was shown that activated CD4 + CD25 ¡ eVector T cells transiently express FoxP3, without having regulatory activity [2,23]. Possibly, the positive prognostic eVect of the presence of FoxP3 + cells in our samples can be attributed to the staining of not only suppressive, but also activated T-lymphocytes expressing FoxP3.…”

Human rhinoviruses induce IL‐35‐producing Treg via induction of B7‐H1 (CD274) and sialoadhesin (CD169) on DC

“…1D). Activation-induced transient FOXP3 expression in human T cells has been frequently observed before [10,[15][16][17] and is not necessarily correlated with regulatory activity [7,10,18].…”

“…Inducible Treg primarily act via soluble mediators and typically produce high levels of immune-suppressive cytokines IL-10 and/or TGF-b. The suppressive function of human inducible Treg seems to be FOXP3-independent [10,11].…”