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

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Vlad G, Ho EK, Vasilescu ER, Fan J, Liu Z, Cai JW, Jin Z, Burke E, Deng M, Cadeiras M, Cortesini R, Itescu S, Marboe C, Mancini D, Suciu-Foca N

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

Transpl Immunol. 2007 Jul;18(1):13-21. Epub 2007 Apr 2.

PubMed ID

17584597 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Aldesleukin	Interleukin-2 receptor subunit alpha	Protein	Humans	Yes	Agonist Modulator	Details