Fiona Powrie

Powrie trabajó con Don Mason en la Escuela de Patología Sir William Dunn estudiando las interacciones de diferentes subconjuntos de células T CD4+ en ratas. Este trabajo identificó que las células T CD4+OX22hi (OX22 es CD45RC en ratas y el equivalente de CD45RB en ratones, ambas isoformas de CD45 ^{[ 6 ]} ) contenían actividad patógena, mientras que las células T CD4 +OX22lo contenían actividad reguladora y podían prevenir la actividad patógena de las células T CD4+OX22hi ^{[ 7 ].} Estos fueron estudios fundamentales y representaron algunos de los trabajos seminales sobre las células T reguladoras (Treg).

Powrie performed post-doctoral studies with Robert L. Coffman at DNAX in Palo Alto, California. Here, she extended her earlier work in rats to mice and developed the "T cell transfer" model, one of the most prominent models of intestinal inflammation where transfer of CD4+CD45RBhi T cells to Rag deficient or SCID mice led to the development of severe intestinal inflammation and wasting disease. This could be prevented by transfer of CD4+CD45RBlo T cells.^[8] Using this model Powrie further identified the pathogenic role played by IFN-γ and TNF-α in intestinal inflammation and the therapeutic potential of IL-10^[9] and highlighted the requirement for TGF-β in the prevention of colitis by the CD4+CD45RBlo regulatory T cell subset^[10] Upon returning to the University of Oxford in 1996, first to the Nuffield Department of Surgery and later, the Sir William Dunn School of Pathology, Powrie used the T cell transfer model to identify the suppressive mechanisms used by regulatory T cells to prevent intestinal inflammation including the requirements for CTLA-4^[11] and the capacity of Treg to prevent colitis driven by innate immune cells as well as CD4+ T cells.^[12] Focusing on pathogenic mechanisms the Powrie lab. identified the critical role played by the cytokine IL-23 in driving pathology in the intestine^[13]

Work from the Powrie lab. identified that Treg could not alone prevent inflammatory bowel disease but could actually cure established inflammation.^[14] Furthermore, Powrie was among the first to identify a population of CD4+CD25+ T cells in human peripheral blood that possessed regulatory capacity, confirming these cells as a bona fide T cell subset in humans.^[15]