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Here we have delineated the phenotype and transcriptional profiles of Treg cells from 18 filarial\u2010infected (Fil<jats:sup>+<\/jats:sup>) and 19 filarial\u2010uninfected (Fil<jats:sup>\u2212<\/jats:sup>) subjects. We found that the frequencies of Foxp3<jats:sup>+<\/jats:sup> Treg cells expressing CTLA\u20104, GITR, LAG\u20103, and IL\u201010 were significantly higher in Fil<jats:sup>+<\/jats:sup> subjects compared with that in Fil<jats:sup>\u2212<\/jats:sup> subjects. Foxp3\u2010expressing Treg\u2010cell populations in Fil<jats:sup>+<\/jats:sup> subjects were also more heterogeneous and had higher expression of IL\u201010, CCL\u20104, IL\u201029, CTLA\u20104, and TGF\u2010\u03b2 than Fil<jats:sup>\u2212<\/jats:sup> subjects, each of these cytokines having been implicated in immune suppression. Moreover, Foxp3\u2010expressing Treg cells from Fil<jats:sup>+<\/jats:sup> subjects had markedly upregulated expression of activation\u2010induced apoptotic genes with concomitant downregulation of those involved in cell survival. To determine whether the expression of apoptotic genes was due to Treg\u2010cell activation, we found that the expression of CTLA\u20104, CDk8, RAD50, TNFRSF1A, FOXO3, and RHOA were significantly upregulated in stimulated cells compared with unstimulated cells. Taken together, our results suggest that in patent filarial infection, the expanded Treg\u2010cell populations are heterogeneous, short\u2010lived, activated, and express higher levels of molecules known to modulate immune responsiveness, suggesting that filarial infection is associated with high Treg\u2010cell turnover.<\/jats:p>","DOI":"10.1002\/eji.201444452","type":"journal-article","created":{"date-parts":[[2014,4,15]],"date-time":"2014-04-15T18:21:04Z","timestamp":1397586064000},"page":"2036-2047","source":"Crossref","is-referenced-by-count":14,"title":["Highly heterogeneous, activated, and short\u2010lived regulatory T cells during chronic filarial infection"],"prefix":"10.1002","volume":"44","author":[{"given":"Simon","family":"Metenou","sequence":"first","affiliation":[{"name":"Laboratory of Parasitic Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health  Bethesda MD 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