In:
Scandinavian Journal of Immunology, Wiley, Vol. 70, No. 3 ( 2009-09), p. 206-215
Abstract:
CD25 monoclonal antibody binding to the α ‐chain of the Interleukin‐2 (IL‐2) receptor, blocks high‐affinity IL‐2 binding, thereby preventing complete T‐cell activation and being of ample importance in transplantation medicine and potentially the treatment of autoimmune disease. However, CD25 antibodies do not only block T‐cell activation but also prevent activation‐induced cell death (AICD) attributing a dual function to IL‐2. In this study, the modulation of the genomic expression profile of human peripheral blood mononuclear cells (PBMC) with therapeutic concentrations of humanized anti‐CD25 mAb was investigated. PBMC were stimulated with CD3 antibody OKT‐3 together with recombinant IL‐2 in the absence or presence of anti‐CD25 mAb. RNA was extracted and subjected to microarray analysis on U133A microarrays (Affymetrix). Anti‐CD25 treatment inhibited several genes typically expressed during T‐cell activation including granzyme B, signalling lymphocyte activation molecule, family member 1 (SLAMF1), CD40‐Ligand (CD40‐L), IL‐9 and interferon (IFN)‐ γ . Interestingly, anti‐CD25 mAb also blocked the expression of several genes important for susceptibility to apoptosis, such as death receptor 6 (DR6) or reversed IL‐2‐mediated repression of anti‐apoptotic genes, such as Fas apoptotic inhibitory molecule 3 (FAIM3)/TOSO. Functional significance of DR6 and TOSO expression in IL‐2‐dependent T‐cell activation was subsequently evaluated by RNA interference in AICD: While siRNA specifically directed against DR6 did not modulate FAS‐L‐mediated apoptosis induction in primary T cells, down‐regulation of TOSO significantly increased susceptibility to apoptosis, emphasizing an important role for TOSO in IL‐2‐mediated AICD.
Type of Medium:
Online Resource
ISSN:
0300-9475
,
1365-3083
DOI:
10.1111/sji.2009.70.issue-3
DOI:
10.1111/j.1365-3083.2009.02281.x
Language:
English
Publisher:
Wiley
Publication Date:
2009
detail.hit.zdb_id:
2020954-X
detail.hit.zdb_id:
120476-2
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