title: Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation.
abstract: The interleukin-2 receptor alpha chain (IL-2Ra, CD25) plays a major part in shaping the dynamics of T cell populations following immune activation, due to its role in T cell proliferation and survival. Strategies to blunt the effector responses in transplantation have been developed by devising pharmaceutical agents to block the IL-2 pathways. However, such strategies could adversely affect the CD25(+)FOXP3(+)T regulatory (T reg) populations which also rely on intereukin-2 signaling for survival. The present study shows that a cohort of heart allograft recipients treated with Daclizumab (a humanized anti-CD25 antibody) display FOXP3 expression patterns consistent with functional T regulatory cell populations. High levels of FOXP3 were observed to correlate with lower incidence of and recovery from acute rejection, as well as lower levels of anti-donor HLA antibody production. Therefore, T reg populations appear fully functional in patients treated with Daclizumab, even when 5 doses were administered. By comparison, patients treated with fewer doses or no Daclizumab had a higher incidence of acute rejection, antibody production and graft failure. Therefore, our data indicates that Daclizumab treatment does not interfere with the generation of regulatory T cells and has a beneficial effect on heart allograft survival.
authors.affiliation: The Department of Pathology, Columbia University, New York, NY 10032, United States.
authors.forename: G
authors.initials: G
authors.lastname: Vlad
authors.forename: E K
authors.initials: EK
authors.lastname: Ho
authors.forename: E R
authors.initials: ER
authors.lastname: Vasilescu
authors.forename: J
authors.initials: J
authors.lastname: Fan
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: J W
authors.initials: JW
authors.lastname: Cai
authors.forename: Z
authors.initials: Z
authors.lastname: Jin
authors.forename: E
authors.initials: E
authors.lastname: Burke
authors.forename: M
authors.initials: M
authors.lastname: Deng
authors.forename: M
authors.initials: M
authors.lastname: Cadeiras
authors.forename: R
authors.initials: R
authors.lastname: Cortesini
authors.forename: S
authors.initials: S
authors.lastname: Itescu
authors.forename: C
authors.initials: C
authors.lastname: Marboe
authors.forename: D
authors.initials: D
authors.lastname: Mancini
authors.forename: N
authors.initials: N
authors.lastname: Suciu-Foca
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006680:HLA Antigens / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006680:HLA Antigens; D053645:Interleukin-2 Receptor alpha Subunit