XXXX and regulatory T cells in @entity2132 .

@entity1 @entity404 @entity2132 @entity1583 @entity403 @entity1199
BACKGROUND: Dysfunction of regulatory T (Treg) cells has been detected in diverse inflammatory disorders, including @entity2132 ( @entity2132 ). @entity1199 is critical for Treg cell growth, survival, and activity. We hypothesized that low-dose @entity1199 could preferentially enhance Treg cells in vivo and suppress clinical manifestations of chronic @entity2132 . METHODS: In this observational cohort study, @entity1 with chronic @entity2132 that was refractory to glucocorticoid therapy received daily low-dose subcutaneous @entity1199 (0.3 10(6), 1 10(6), or 3 10(6) IU per square meter of body-surface area) for 8 weeks. The end points were safety and clinical and immunologic response. After a 4-week hiatus, @entity1 with a response could receive @entity1199 for an extended period. RESULTS: A total of 29 @entity1 were enrolled. None had progression of chronic @entity2132 or relapse of a @entity1583 . The maximum tolerated dose of @entity1199 was 1 10(6) IU per square meter. The highest dose level induced unacceptable constitutional symptoms. Of the 23 @entity1 who could be evaluated for response, 12 had major responses involving multiple sites. The numbers of @entity404 + Treg cells were preferentially increased in all @entity1 , with a peak median value, at 4 weeks, that was more than eight times the baseline value (P<0.001), without affecting @entity404 + conventional T (Tcon) cells. The Treg:Tcon ratio increased to a median of more than five times the baseline value (P<0.001). The Treg cell count and Treg:Tcon ratio remained elevated at 8 weeks (P<0.001 for both comparisons with baseline values), then declined when the @entity1 were not receiving @entity1199 . The increased numbers of Treg cells expressed the transcription factor @entity403 ( @entity403 ) and could inhibit autologous Tcon cells. Immunologic and clinical responses were sustained in @entity1 who received @entity1199 for an extended period, permitting the glucocorticoid dose to be tapered by a mean of 60% (range, 25 to 100). CONCLUSIONS: Daily low-dose @entity1199 was safely administered in @entity1 with active chronic @entity2132 that was refractory to glucocorticoid therapy. Administration was associated with preferential, sustained Treg cell expansion in vivo and amelioration of the manifestations of chronic @entity2132 in a substantial proportion of @entity1 . (Funded by a Dana-Farber Dunkin' Donuts Rising Star award and others; ClinicalTrials.gov number, NCT00529035.).
