Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation

• Published in: Transplant immunology Vol. 18; no. 1; pp. 13 - 21
• Main Authors: Vlad, G, Ho, E.K, Vasilescu, E.R, Fan, J, Liu, Z, Cai, J.W, Jin, Z, Burke, E, Deng, M, Cadeiras, M, Cortesini, R, Itescu, S, Marboe, C, Mancini, D, Suciu-Foca, N
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2007
• Subjects: Adolescent; Adult; Aged; Allergy and Immunology; Daclizumab; Female; Forkhead Transcription Factors - analysis; FOXP3; Heart transplantation; Heart Transplantation - immunology; HLA Antigens - immunology; Humans; Interleukin-2 Receptor alpha Subunit - antagonists & inhibitors; Male; Middle Aged; Rejection; T regulatory cells; T-Lymphocytes, Regulatory - immunology; Rejection; Daclizumab; T regulatory cells; FOXP3; Heart transplantation
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2007.03.001

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.