J.D. Fontenot et al., "Regulatory T cell lineage specification by the forkhead transcription factor Foxp3," Immunity, 22:329-41, 2005. (Cited in 217 papers)
Using a GFP-tagged knockin mouse, Alexander Rudensky's group at the University of Washington in Seattle showed that the expression of the transcription factor Foxp3 defines a subset of regulatory T cells involved in suppressing autoimmune activity.
Unlike most other transcription factors, which are expressed in multiple systems or tissues, Foxp3 was found only in a subset of αβ T cells. "It's a very rare instance when there is a dedicated function," Rudensky says. At the time, CD25 expression was the best available marker for identifying regulatory T cells; Foxp3's surprising specificity has since made it a more reliable marker.
Rudensky and his colleagues found that Foxp3 expression not only defines regulatory T cells, but is also necessary for the suppressor function of these cells. This year Rudensky and several other groups published a list of Foxp3's genetic targets, which could help explain why the loss of the gene is catastrophic (see www.the-scientist.com/news/display/42904).
The work ahead:
Foxp3 expression could have additional functions, points out Fred Ramsdell of ZymoGenetics in Seattle. During T-cell activation there is a transient expression of Foxp3. "Some of those cells may go off to become regulatory T cells or some may not," Ramsdell says. "It's not clear and still needs to be worked out."
|Top-Cited "Foxp3" studies:|
|S. Hori et al., Science, 299: 1057-61, 2003. (cited in 946 papers)|
|J.D. Fontenot et al., Nat Immunol, 4: 330-6, 2003. (cited in 846 papers)|
|R. Khattri et al., Nat Immunol, 4: 337-42, 2003. (cited in 599 papers)|